StemCell Therapy

Since PDS Biotechnology Corporation (NASDAQ:PDSB) and Axsome Therapeutics Inc. (NASDAQ:AXSM) are part of the Biotechnology industry, they are influenced by contrast. The influences particularly affect the dividends, analyst recommendations, profitability, institutional ownership, risk, earnings and valuation of both companies.

Earnings & Valuation

Demonstrates PDS Biotechnology Corporation and Axsome Therapeutics Inc. earnings per share, gross revenue and valuation.

Profitability

Table 2 demonstrates the return on equity, net margins and return on assets of PDS Biotechnology Corporation and Axsome Therapeutics Inc.

Risk & Volatility

PDS Biotechnology Corporation has a 2.42 beta, while its volatility is 142.00% which is more volatile than Standard and Poors 500. From a competition point of view, Axsome Therapeutics Inc. has a 2.65 beta which is 165.00% more volatile compared to Standard and Poors 500.

Liquidity

PDS Biotechnology Corporations Current Ratio is 5 while its Quick Ratio is 5. On the competitive side is, Axsome Therapeutics Inc. which has a 5.7 Current Ratio and a 5.7 Quick Ratio. Axsome Therapeutics Inc. is better positioned to pay off short and long-term obligations compared to PDS Biotechnology Corporation.

Analyst Ratings

The next table highlights the given recommendations and ratings for PDS Biotechnology Corporation and Axsome Therapeutics Inc.

The consensus target price of PDS Biotechnology Corporation is $8.5, with potential upside of 201.42%. Competitively Axsome Therapeutics Inc. has a consensus target price of $48, with potential upside of 5.66%. The information presented earlier suggests that PDS Biotechnology Corporation looks more robust than Axsome Therapeutics Inc. as far as analyst belief.

Insider & Institutional Ownership

Roughly 28.3% of PDS Biotechnology Corporation shares are owned by institutional investors while 46.3% of Axsome Therapeutics Inc. are owned by institutional investors. About 6.5% of PDS Biotechnology Corporations share are owned by insiders. Comparatively, Axsome Therapeutics Inc. has 2.2% of its share owned by insiders.

Performance

In this table we provide the Weekly, Monthly, Quarterly, Half Yearly, Yearly and YTD Performance of both pretenders.

For the past year PDS Biotechnology Corporation has weaker performance than Axsome Therapeutics Inc.

Summary

On 6 of the 11 factors Axsome Therapeutics Inc. beats PDS Biotechnology Corporation.

Axsome Therapeutics, Inc., a clinical-stage biopharmaceutical company, develops therapies for the management of central nervous system (CNS) disorders. The companys product candidates include AXS-05 that is in Phase III trial for the treatment of treatment resistant depression and Alzheimers disease agitation; and AXS-02, which is in Phase III trial to treat complex regional pain syndrome, knee osteoarthritis related to bone marrow lesions, and chronic low back pain related to Modic changes. It is also developing AXS-06, a preclinical product candidate for CNS disorders, including chronic pain. The company was founded in 2012 and is based in New York, New York.

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Comparison of PDS Biotechnology Corporation (PDSB) and Axsome Therapeutics Inc. (NASDAQ:AXSM) - The Broch Herald

It's easy to give thoughtless gifts. This year, give thoughtful gifts: science gifts! They're experimentally validated as wonderful*. This is Massive's 2019 holiday science shopping guide, with cool stuff from all around the science web, for Thanksgiving, Black Friday, Christmas, and beyond.

Illustrated by Matteo Farinella, Designed by Allan Lasser

Massive Science

Oh wow, so weird to see us at the top here. The coolest thing on this list is definitely the Women of Science Tarot deck we made. The deck features is itself a work of art, with beautiful original work from Matteo Farinella. Instead of the traditional face cards of many tarot decks, instead there are portraits of important women in science's history, including Mae Jemison, Rachel Carson, Marie Curie, Ada Lovelace, and more. If the the $75 price tag is too steep, there are also postcard packs with art from the deck and posters!

Genius Games

The geniuses at Genius Games make science-themed board games and card games. In Virulence, take on the role of a virus and replicate. Build atoms in Subatomic. Or, become the world's first programmers in Lovelace & Babbage. Massive has partnered with Genius Games to offer a 20% off coupon, just use the code MassiveScience20!

Courtesy of Genius Games

Two Photon

The undisputed champion of science art, pins, jewelry, and more. Our favorites include the neuroscience section, with brain pins and neuron necklaces, the virus t-shirt, and the nameplate necklaces, with options like "Scientist", "Doctor", and "Programmer."

Stitching Hew

What really sets Stitching Hew apart are their intricate stitch patterns, especially the Brainbrow Pyramidal Neuron Print, detailed enough to make Cajal blush. There are even downloadable stitch patterns or an entire beginner's science hand embroidery kit.

Rachel Ignotofsky

The prolific author and illustrator made one of our favorite books, Women in Science: 50 Fearless Pioneers Who Changed the World. But she also has other books, like Women in Art: 50 Fearless Creatives Who Changed the World, along with a whole pile of beautiful art prints to choose from.

Science On A Postcard

If you're looking for an enamel pin to signal your allegiance to a particular scientific field, then this Etsy shop is for you! Packed with notebooks, postcards, stickers and an even a pocket mirror, the Science On A Postcard shop hosts some of our favourite pins, including ones that say science communicator, future scientist and that climate change is real.

Awkward Yeti

You've undoubtedly seen their comics all over the great wide web, but Awkward Yeti's store is packed with goodies. There's tabletop games for the gamer who loves organs, some of the best stuffed organs (okay, the only stuffed organs) we've seen, like a uterus and an irritable bowel, and prints from the comic.

Courtesy of Awkward Yeti

Waterlust

You don't have to be a marine scientist to love their products. Waterlust carries leggings (with pockets!), rashguards and swim tops, board shorts, and more for people who love being in the water. Their products are great on land too the fabric is soft and stretchy, and the leggings and shorts have a wide waistband that makes them incredibly comfortable for lounging around the house or going to the gym. Each pattern is dedicated to a specific marine conservation cause (my favorite is the Floridian Aquifer collection). Their products are partially made from recycled plastic bottles and the gear is shipped in eco-friendly packaging, making Waterlust a great choice for the outdoor enthusiasts in your life!

PurpleLilacAmigurumi

This science crochet shop is run by a PhD student at the University of Toronto, so you know the plushies are accurate. Oh and they're lovely too. Take the crocheted neuron necklace, or our personal favorite, the Islets of Langerhans crochet pattern.

Skype a Scientist

Skype a Scientist is one of the best science outreach organizations we know of and they have the merch to match. If you love snakes and also Greek myths, consider this Medusa-as-a-scientist t-shirt. Or rather, if you're more of an astrobiology person, maybe the hardy tardigrade is more your speed.

The Vexed Muddler

If you're interested in science-themed underwear, this is the store for you. Consider the Maratus volans (aka the peacock spider) boxer briefs, which to be honest are kind of terrifying. If that's not your thing they also have phylogenetic tree skirts, intergalactic space dresses, and oh what the heck here's black widow underwear.

Slow Dance

Perhaps something a bit more...meditative? Slow Dance is a frame that produces slow-motion, real-time movement. The creators say it helps lower stress and is quite good for meditation (we weren't just being cute).

*data not shown

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Researchers who collaborate with top scientists early on do better in their lifelong career - Massive Science

Using immunotherapy with genetically modified T cells that express chimeric antigen receptors or CARs designed to target tumor-associated molecules, have impressive efficacy in the treatment hematological malignancies.

A CAR is a synthetic construct that, when expressed in T cells, mimics T cell receptor activation and redirects specificity and effector function toward a specified antigen.[1]

In the treatment of cancer, this process is accomplished by linking an extracellular ligand-binding domain specific for a tumor cell surface antigen to an intracellular signaling module that activates T cells upon antigen binding.[1]

The presented studies include results from emerging second-generation cellular immunotherapy products that strive to overcome the limitations of existing products such as resistance and reduce toxicity and simplify treatment.

Cellular immunotherapy uses genetic engineering to enhance the ability of the immune system the bodys defense system against infection and disease to kill malignant cells in the blood, the bone marrow, and other sites, in order to keep cancer from coming back.

CAR T-cell TherapyChimeric antigen receptor T-cell therapies, better known as CAR T-cell therapies, are developed by harvesting a patients own T-cells, the immune systems primary cancer-killing cells, engineering them to target proteins specific to the surface of cancer cells, and reintroducing these modified T-cells back into the patients immune system to kill the cancer cells.

First generationFirst-generation CAR T-cell therapies primarily target CD-19, a protein found on the surface of most normal and malignant B cells in B cell cancers such as lymphoma. These therapies have been shown to produce long-term remissions in about one-third of patients with B-cell lymphomas that have not responded to prior therapies.

We are now seeing efforts to enhance the effectiveness of CAR T-cell therapy by designing products capable of attacking multiple targets, expand the availability of cellular immunotherapy to other blood cancers such as multiple myeloma and replace the complex manufacturing process required for CAR T-cell therapy with a uniform off-the-shelf product, noted Gary Schiller, MD, UCLA Health, an academic medical center which includes a number of hospitals and an extensive primary care network in the Los Angeles, California, region.

One of the phase I studies evaluates an off-the-shelf cellular immunotherapy product that targets two proteins found on the surface of lymphoma cells, including its potential to revive previously administered CAR T-cells that have stopped working.

Another study presents preclinical results for one of the first cellular immunotherapies to be based on off-the-shelf natural killer (NK) cells and the first, according to its manufacturer, to be genetically engineered to contain three active anti-tumor components.

The other two studies, also phase I studies, assess novel CAR T-cell therapies for multiple myeloma that test different dual-target strategies.

One investigational agent is genetically engineered to contain two proteins that attach to BCMA, a protein found almost exclusively on the surface of plasma cells, the immune-system cells that become cancerous in multiple myeloma.

The other is designed to target both BCMA and CD-38, another protein found on the surface of plasma cells. In both studies, many patients achieved minimal residual disease (MRD) negativity, which means that using highly sensitive testing fewer than one myeloma cell per 100,000 cells was identified in the bone marrow. Previous studies have shown that patients who achieve this milestone have a lower risk of relapse after more than three years of follow-up.

Dual-targeted CAR T-cell therapiesThe three phase I studies also hint at the possibility that dual-targeted CAR T-cell therapies might result in fewer patients experiencing moderate to severe cytokine release syndrome (CRS), a known adverse effect caused by an immune response in the body to the activated T cells that are attacking the cancer. CRS causes flu-like symptoms such as fever, body aches, and fatigue, and in severe cases can be life-threatening. Treatment with the drug tocilizumab can reduce CRS symptoms.

Dual-Targeted Antibody Elicits Durable ResponsesPatients with B-cell Non-Hodgkin Lymphoma (NHL) that had returned after or failed to respond to a median of three prior therapies showed complete responses (CR) and durable remissions after being treated with an investigational drug called mosunetuzumab (RG7828; Genentech/Roche). [2]

This investigational agent is a humanized, T-cell bispecific antibody designed to engage T cells and redirect their cytotoxic activity against malignant B cells. The drug works by activating the patients own T-cells, stimulating them to attack and kill cancerous B cells to which they have been introduced by the novel antibody.

Mosunetuzumab simultaneously binds to CD3 epsilon (CD3), a component of the T-cell receptor (TCR) complex, and to CD20, a B-cell surface protein expressed in a majority of B-cell malignancies. This results in crosslinking of the TCR, inducing downstream signaling events that leads to B-cell killing.

Among patients whose lymphoma progressed after treatment with CAR T-cell therapy, 22% had complete remissions when treated with mosunetuzumab. This new drug targets two proteins, one on the surface of tumor cells and the other on the surface of the recipients Tcells.

Unlike CAR T-cell therapy, mosunetuzumab is an off-the-shelf immunotherapy product that can be given to patients without having to genetically modify their T cells, noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T-cell therapy, he added.

The researchers observed many remissions continue after patients stop receiving the drug.

I have stopped therapy in some patients after six months and they have remained in remission. Some patients have remained in remission without additional therapy for more than a year, Schuster said.

New treatment options are needed not only for patients in whom CAR T-cell therapy has failed, but also for those patients whose lymphomas are getting worse so quickly that they cannot wait for CAR T-cell manufacturing, which takes several weeks, Schuster explained.

The data presented during the annual meeting of the American Society of Hematology included 270 patients (median age 62, 172 men) enrolled in the phase I trial in seven countries (the United States, Australia, Canada, Germany, South Korea, Spain, and the United Kingdom). All participating patients had B-cell lymphomas that had come back or not responded to a median of three prior therapies. Two-thirds of patients (67%) had fast-growing lymphomas; 85 (31%) patients had more slow-growing forms of the disease. In 30 patients (11%), the cancer was resistant to or returned after an initial response to CAR T-cell therapy; in 77 patients (29%), the disease had progressed after a stem cell transplant.

All patients were treated with mosunetuzumab by intravenous infusion. They had an imaging test at either six weeks or three months after starting therapy to assess the initial response to treatment, and responses continued to be followed every three months thereafter.

Forty-six of 124 patients with fast-growing lymphomas (37%) had measurable decreases in the extent of their cancer (objective response); 24 of 124 patients (19%) saw all detectable tumors disappear (complete response). A higher response rate was observed in patients with higher exposure to mosunetuzumab. Among patients with slow-growing lymphomas, 42 of 67 (63%) had objective responses and 29 of 67 (43%) had complete responses. Both objective response rate and complete response rate were maintained in subgroups of patients at high risk for relapse.

Complete remissions appear to be long lasting, Schuster said.

With a median follow-up of six months since first complete remission, 24 of 29 patients (83%) who achieved complete remissions of their slow-growing lymphomas and 17 of 24 patients (71%) who achieved complete remissions of their fast-growing lymphomas remain free of disease. In some patients whose cancers progressed after receiving CAR T-cell therapy, highly sensitive molecular testing showed that the previously administered CAR T cells increased in number.

This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR-T treatment, Schuster noted.

Cytokine-release syndromeIn this study, 29% of patients treated with mosunetuzumab experienced cytokine-release syndrome that was mostly mild.

Cytokine release syndrome or CRS is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. While most patients have a mild reaction, sometimes patients may have a severe, life threatening, reaction.

In 3% of patients, CRS was treated with tocilizumab (Actemra; Genentech/Roche). Four percent of patients experienced moderately severe neurologic side effects. Patients who received higher doses of mosunetuzumab were no more likely to have CRS or neurologic side effects than patients treated at lower doses.

A study of a higher dose of mosunetuzumab is now enrolling patients and long-term follow-up of these patients will ultimately help to better evaluate the durability of response data.

Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents, Schuster concluded.

Novel Off-the-Shelf CARPreclinical studies provide the first evidence that cellular immunotherapy for B cell cancers could ultimately become an off-the-shelf product, capable of being uniformly manufactured in large quantities as prescription drugs are.

We have taken the concept of traditional pharmaceutical drug development and applied it to cellular therapy, explained senior author Bob Valamehr, Ph.D, of Fate Therapeutics, a San Diego biopharmaceutical company.

The product called FT596, is among the first cellular immunotherapies to be based on off-the-shelf NK cells the first line of defense of the immune system and is the first cellular immunotherapy to be genetically engineered to contain three active anti-tumor components, Valamehr explained.

Comparable with standard CAR T-cell therapyFT596 demonstrated comparable ability to kill cancerous white blood cells as standard CAR T-cells and, when combined with the drug rituximab (Rituxan; Genentech/Roche), killed cancerous white blood cells that were no longer responding to standard CAR T-cell therapy due to loss of the CD19 antigen target.

The U.S. Food and Drug Administration (FDA) approved Fate Therapeutics Investigational New Drug Application for FT596 in September 2019 and the company hopes to begin a first-in-human phase I clinical trial for the treatment of B-cell lymphoma and chronic lymphocytic leukemia in the first quarter of 2020.

The primary purpose of this trial will be to assess the safety and activity of FT596 in patients.

ManufacturingThe development and manufacturing of FT596 begins with human induced pluripotent stem cells (iPSCs) that are uniquely capable of unlimited self-renewal and can differentiate into more than 200 types of human cells. These iPSCs are genetically engineered, after which a single genetically engineered cell or clone is selected and multiplied in the laboratory to create a master engineered cell line that can be repeatedly used to generate cancer-fighting immune-system cells such as NK and T cells.

Natural Kiler Cells or NK cells are a type of lymphocyte and a component of innate immune system, the bodys first line of defense against infection and disease. Unlike T-cells, which have to be trained to recognize their target and can kill only cells that display that target on their surface, NK cells do not need special preparation before going on the attack and can kill many different types of transformed or infected cells.

NK cells are multifaceted and can be viewed as a jack-of-all-trades when it comes to protecting the host, whereas T cells can act in only one way, Valamehr explained.

But NK cells are also different in other ways. They are inherently limited in their capacity to multiply and expand when infused into patients, and they have a shorter lifespan.

Valamehr and his colleagues used genetic engineering to address these shortcomings. In addition to engineering FT596 to carry a CAR targeting the CD19 protein, which is produced by nearly all B-cell lymphomas and leukemias, they inserted two other novel proteins: CD16, which boosts and broadens the NK cells ability to kill cancer cells, and IL15, which stimulates FT596 to proliferate and persist.

Valamehr explained that FT596 has been designed to address two more limitations of CAR T-cell therapy .

The investigational agent is an off-the-shelf product. As a result, it significantly improves the current patient-by-patient CAR T-cell treatment paradigm by eliminating the time-consuming and costly process that is currently required to treat a patient with CAR T-cells.

The addition of the CD16 protein gives FT596 broader therapeutic activity and versatility. In combination with rituximab, FT596 has the potential to lead to deeper and more durable responses and overcome resistance that hampers the long-term efficacy of CAR T-cell therapy.

Eliminating the high production cost, weeks of manufacturing time, and complex manufacturing process required for CAR T-cell therapy and replacing it with a mass-produced, off-the-shelf product, promises to expand access to effective cell-based cancer immunotherapy to many more patients who may benefit from it, Valamehr concluded.

Results from CARTITUDE-1 in R/R Multiple MyelomaPatients with multiple myeloma who had received a median of five prior therapies, and for whom standard-of-care treatments were no longer working, had a high response rate when treated with the investigational CAR T-cell therapy JNJ-68284528 (JNJ-4528), which targets BCMA, a protein commonly found on the surface of multiple myeloma cancer cells.

These patients participated in a clinical trials (NCT03548207), supported by Janssen Research & Development, designed to characterize safety of and establish the recommended Phase II dose (RP2D) (Phase Ib) and to evaluate the efficacy of JNJ-68284528 (Phase II).

We are seeing a high response rate, with most patients achieving MRD negativity, noted lead study author Deepu Madduri, MD, of The Tisch Cancer Institute at Mount Sinai in New York.

Considering these patients have all received multiple prior therapies, these results are extremely encouraging, Madduri added.

All evaluable patients receiving this CAR T-cell therapy have achieved MRD-negative disease state and 27 of 29 patients are progression free at a median follow-up of six months, Madduri said.

Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection. Typical signs and symptoms of multiple myeloma may be bone pain or fractures, high levels of calcium in the blood, kidney damage, and anemia. Multiple myeloma affects an estimated 160,000 people each year, occurs most often in people over 60. The disease is slightly more common in men than in women.

Although new therapies for multiple myeloma have recently become available that can extend patients life expectancy, a cure for the disease remains elusive.

We can get the disease into remission, but most patients unfortunately relapse, and outcomes are very poor for patients who have relapsed multiple times, she said.

Researchers explained that JNJ-4528 is a novel CAR T-cell therapy featuring two molecules that bind to BCMA, a protein found on the surface of multiple myeloma cells.

We are learning that every CAR T-cell therapy is different, Madduri said.

JNJ-4528 has a unique CAR T-cell composition in patients, preferentially enriched in CD8 T cells, which are believed to be one of the most important T cells in killing cancer cells, she noted.

This phase Ib/II trial is continuing to enroll patients.

During the 2019 annual meeting of the American Society of Hematology, Madduri reported results for the first 29 patients enrolled.

Patients T-cells were collected and sent to a laboratory where they were genetically engineered to express JNJ-4528. Prior to re-infusing these CAR T-cells, the patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells.

Following chemotherapy, each patient received a single infusion of the JNJ-4528 CAR T-cells.

After a minimum of 28 days, these patients had blood and bone marrow exams, which was followed by exams at six months, and one year after treatment to assess their response. The primary aims of the trial are to assess the therapys safety and to confirm the dose to be tested in a larger, phase II trial.

The median follow-up time in the current analysis is six months. Overall, 100% of patients had a clinical response to JNJ-4528. Moreover, 66% had a stringent complete response, meaning that sensitive laboratory and microscopic tests found no evidence for myeloma proteins or cells in blood, urine, or bone marrow.

Most patients (93%) experienced some form of CRS. One patient had severe (grade 3) CRS, and one patient died from its complications 99 days after the CAR T-cell infusion. In 76% of patients, CRS was treated with tocilizumab.

To see some patients in this heavily pretreated population surviving for a year or more with a one-time treatment and a manageable safety profile is remarkable, Madduri explained.

These patients feel that they have their quality of life back. They no longer have to come into the clinic for weekly treatments and some are well enough to travel, Madduri concluded.

The phase II portion of this study is ongoing to evaluate the overall response rate of patients treated with JNJ-68284528 (JNJ-4528). Additional clinical studies are evaluating the safety and efficacy of JNJ-4528 in different multiple myeloma treatment settings.

BreakthroughEarlier this week the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528).

The granting of Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528) is a significant milestone as we continue to accelerate the global development of this innovative CAR-T therapy in collaboration with Legend Biotech, noted Sen Zhuang, MD, Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development.

We look forward to continuing to work closely with the U.S. Food and Drug Administration to advance the clinical development program for JNJ-68284528 (JNJ-4528) and ultimately bring this BCMA-targeted immunotherapy to patients living with multiple myeloma who are in need of a new therapeutic option, Zhuang concluded.

Encouraging Results for Dual-Targeted CAR T-Cell TherapyMore than three out of four patients with multiple myeloma that returned or did not respond to at least two therapies remained in remission seven months after treatment with a novel CAR T-cell therapy targeting two proteins that are frequently found on myeloma cells.

Nine patients experiencing sustained remissions in this study, which ws supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project fund of Hubei Province of China, and Cellyan Therapeutics, were diagnosed with a difficult-to-treat form of multiple myeloma in which the disease has spread beyond the bone marrow.

Roughly one in 10 patients with multiple myeloma develop tumors in the organs or soft tissues such as the blood vessels, muscles, and nerves. These so-called extramedullary tumors respond poorly to treatment, and patients who develop them have a poor outlook and poor health related quality of life (hrQoL)

Our results show that this CAR T-cell product can effectively achieve elimination of extramedullary tumors, said study author Yu Hu, MD, Ph.D, of Union Hospital, Huazhong University of Science and Technology in Wuhan, China.

Although these are preliminary data, they are encouraging for patients with multiple myeloma who have not responded to other therapies, Hu added.

Hu and his colleagues are developing the first CAR T-cell therapy to be genetically engineered to target BCMA and CD38, two proteins found on the surface of plasma cells. Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection and disease.

Our thinking was that targeting both of these proteins would improve treatment efficacy without increasing toxicity, and induce deeper, more durable remissions, Hu noted.

The first-in-humans phase I trial enrolled 22 patients whose average age was 59, of whom 11 were men. All had multiple myeloma that had returned or not responded to at least three therapies. Nine of the 22 patients had extramedullary tumors. The study aims were to determine the safest and most effective dose of the CAR T-cell therapy as well as to initially evaluate its effectiveness.

Just like in other trials with CAR T-cell therapies, the participating patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells. Then each patient was infused with the dual-targeted CAR T cells. Patients were divided into five groups, with each group receiving a higher dose than the previous one. Depending on the cell dose, patients received either one or two infusions.

At a median of 36 weeks of follow-up, 18 patients (90.9%) had MRD-negative disease. Twelve patients (54.5%) had a stringent complete response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a good or very good partial response, meaning that the level of M-protein (an abnormal protein produced by cancerous plasma cells) in the blood or urine was reduced but still detectable. In eight of the nine patients with extramedullary lesions, these tumors were undetectable on their computed tomography scans. For the 17 patients who remained in remission at seven months after treatment, the median duration of response was 28.8 weeks.

The adverse events observed included 20 patients who experienced CRS, of whom six needed treatment. No serious adverse neurologic effects such as seizures, movement impairment, difficulty speaking or understanding speech, or fatal swelling in the brain were reported.

With this dual-targeted CAR T-cell therapy, we have demonstrated a high response rate, especially a higher rate and longer duration of stringent complete response, compared with other therapies, as well as effective elimination of extramedullary lesions, with no serious neurologic adverse effects and manageable levels of other adverse effects, Hu concluded.

The investigators continue to follow the patients for the next two years. They are also planning to conduct a phase II trial in both China and the United States to test the treatments effectiveness in a larger number of patients.

Clinical trialsA Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1) NCT03548207

References[1] Srivastava S, Riddell SR. Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy. J Immunol. 2018;200(2):459468. doi:10.4049/jimmunol.1701155 [Abstract][2] Schuster SJ, Bartlett NL, Assouline S, Yoon SS, Bosch F, Sehn LH, Cheah CY, Shadman M, et al. Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines. 61st annual meeting of the American Society of Hematology. Program: General Sessions. Session: Plenary Scientific Session. Hematology Disease Topics & Pathways: antibodies, Follicular Lymphoma, CRS, Diseases, Biological, Therapies, neurotoxicity, Adverse Events, CAR-Ts, Non-Hodgkin Lymphoma, DLBCL, immunotherapy, Lymphoid Malignancies. [Abstract][3] Goodridge JP, Mahmood S, Zhu H, Gaidarova S, Blum R, Bjordahl R, Cichocki F, et al. FT596: Translation of First-of-Kind Multi-Antigen Targeted Off-the-Shelf CAR-NK Cell with Engineered Persistence for the Treatment of B Cell Malignancies. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 625. Lymphoma: Pre-ClinicalChemotherapy and Biologic Agents: Targeting Apoptosis Pathways in Lymphoma.[Abstract][4] Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, Allred AJ, Banerjee A, et al. Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM). 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Novelty in CAR T in Relapsed/Refractory Multiple Myeloma. [Abstract][5] Li C, Mei H, Hu Y, Guo T, Liu L, Jiang H, Tang L, Wu Y, et al. A Bispecific CAR-T Cell Therapy Targeting Bcma and CD38 for Relapsed/Refractory Multiple Myeloma: Updated Results from a Phase 1 Dose-Climbing Trial61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Therapy for Relapsed Myeloma. Hematology Disease Topics & Pathways: Biological, Diseases, Adult, Therapies, Lymphoma (any), Adverse Events, CAR-Ts, Elderly, Biological Processes, Technology and Procedures, Cell Lineage, Study Population, Clinically relevant, Lymphoid Malignancies.

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ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment - OncoZine

Eating a very low-calorie diet is an unpleasant but effective way to live longer, prevent age-related diseases and even improve the immune systems function. A new study in mice finds that a compound used in herbal medicine can give a similar immune boost if given before vaccination no dieting required.

Ina new paper inScience Signaling, researchers at the University of Hyderabad in India and Cornell University College of Veterinary Medicine show that a compound called halofuginone improves the immune response to a potential vaccine against dengue virus. Halofuginone tricks the body into thinking it is starving for amino acids, which activates a pathway that results in more, and better, antibodies that are better able to neutralizing the virus. With additional testing, the compound could be part of a strategy to improve the effectiveness of vaccines for diseases such as dengue, which have been difficult to control.

Avery August

The research group was led by Avery August, vice provost for academic affairs and Howard Hughes Medical Institute professor of immunology, and included graduate students Sabrina Solouki and Jessica Elmore, in collaboration with Weishan Huang, adjunct assistant research professor of Microbiology and Immunology, and Nooruddin Khan, assistant professor of biotechnology at the University of Hyderabad in India.

From previous studies, they knew that halofuginone activates a pathway called the amino acid starvation response, which normally kicks in when the body is starved of proteins. Restricting calories can have multiple impacts on the immune system, and the researchers wanted to know how artificially activating this pathway would affect immune response to a vaccine.

Weve been studying the pathway using a compound called halofuginone, which is a natural product found in plants, August said. Halofuginone is a component of an herb used in Chinese medicine. It shows potential for treating muscular dystrophy, autoimmune disease and certain cancers and appears to have few side effects. It mimics amino acid starvation in the body by blocking the enzyme that links amino acids to the molecules that deliver them to the site of protein production.

Members of Augusts lab have been experimenting with different mixes of dengue proteins to develop a better vaccine, so dengue was a natural choice for testing the immune effects of halofuginone. The World Health Organization lists dengue among its top 10 threats to global health and about half the worlds population is at risk of contracting the virus. It is transmitted by mosquitoes and causes flu-like symptoms in most people, but in about 20 percent of cases, the infection progresses into severe dengue, which can cause shock, hemorrhaging or death.

The virus has been especially difficult to control, in part, because there is no vaccine suitable for individuals who have not already been exposed. A vaccine developed by Sanofi and tested in the Philippines in 2017 successfully protected individuals who had already been exposed to the virus, but increased the risk of severe dengue in previously unexposed children. Currently, the pharmaceutical company Takeda is testing a new dengue vaccine in a multi-country clinical trial. Initial results are promising, but it is unknown whether the new vaccine will also increase the risk of severe dengue in unexposed individuals.

In the current study, researchers injected some mice with halofuginone and some with an innocuous salt solution, then inoculated all of the mice with a potential dengue vaccine. Then they looked for differences in the immune response to the vaccine in the two groups.

Mice that received halofuginone produced twice as many antibodies against the virus compared to mice that only received the vaccine, and these antibodies bind to dengue viral components more strongly. Mice dont contract dengue, so the researchers couldnt test whether they were protected. But when they tested the efficacy of the antibodies against dengue virus in a test tube, they saw that halofuginone resulted in antibodies that more effectively neutralized the virus. We were particularly surprised by the quality of the antibody response which is the important part, August said. In this case the actual affinity of the antibodies for the virus particles was enhanced by the halofuginone.

Furthermore, the researchers showed that halofuginone works specifically by encouraging the formation of germinal centers in the lymph nodes and spleen. Germinal centers act like factories to produce the B cells that pump out antibodies, and memory B cells that persist for decades and restart antibody production if the invader returns.

This pathway hasnt before been thought of as one that can regulate enhancing vaccine memory, said August. It allows us potentially to enhance the bodys memory specifically for that vaccine.

Halofuginone worked equally well to enhance the immune response against the four types of dengue virus, but this approach likely would boost any vaccine.

Of course, before a shot of halofuginone becomes part of a standard vaccine regimen, the compound will need to be further tested for safety and effectiveness in humans. These experiments used doses of halofuginone that are larger than what people typically ingest through herbal medicine practices. Additionally, the researchers have not yet screened for side effects on other organ systems in the mice, but plan to explore this area in the future.

This study primarily focused on B cells that produce antibodies against invading pathogens, but now Augusts group and their collaborators are examining the specific effects of halofuginone on the response of T cells, which detect the presence of invaders, kill infected cells and signal B cells to create antibodies.

Overall, the findings suggest that investigating drugs that mimic starvation may be a promising area of research for finding strategies to enhance vaccine effectiveness, especially for dengue and other diseases that still lack approved vaccines.

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Simulating amino acid starvation may result in better vaccines for dengue and other infections - Jill Lopez

The cornerstone of managing any disease, especially the complicated ones like diabetes, is early diagnosis and access to treatment. In case of this hormonal disorder, early diagnosis is extremely essential because it is like to affect your immune function badly. According to a study by Case Western Reserve University School of Medicine in Cleveland, uncontrolled diabetes makes it difficult for people affected by the condition to avoid infections. High sugar levels in their blood can unleash destructive molecules that interfere with the bodys natural infection-control mechanism, says the study.

When your your blood sugar levels go for a toss, every cell of your body gets severely damaged. In fact, diabetes can affect your crucial organs too. These damages drive your body into an immune response mode leading to inflammation. Prolonged inflammation leads to various kinds of diseases including obesity.

In case of excessive cell and tissue damage in your body, the immune cells are likely to go on an overdrive mode. Under normal circumstances, the macrophages (white blood cells which are part of your immune system) clear the cellular debris to battle any kind of tissue damage. They also wipe out foreign substances, microbes, cancer cells, and everything else that arent healthy to body cells. When there is too much damage happening and that too for a prolonged period of time, the macrophages go on an overdrive and kill the healthy cells leading to inflammation. That is why you need to keep your blood sugar levels in check, if you need a healthy immune system.

Your bodys natural defence mechanism needs to be taken care of, so that it doesnt go weak. The best way to do so is having the right foods and exercising regularly. Having ayurvedic herbs and formulas will also go a long way in revving up your immune system. Heres a list of foods and formulas to keep you strong through these winter days.

Dabur has long been using the wisdom of Ayurveda through its formulas to give us effective, natural, side-effect-free solutions for conditions that are tough to treat. Dabur Sugar-Free Chawanprakash is the best example of such an ayurvedic remedy. This all-natural product, made from more than 45 trusted Ayurvedic ingredients like Amla, Ashwagandha, Guduchi etc., modulates the activity of natural killer cells and cytokines to strengthen your bodys defence mechanism. Amla, which is an extremely rich source of Vitamin C, helps in amping up immunity. Chyawanprakash reduces the activation of a complement pathway which gets activated in case of an allergic inflammation, damaging the surrounding cells. It also increases the activity of immune cells called macrophages. These cells play a role in triggering non-specific immune responses and further reduce chances of infections. Apart from this, Dabur Chawanprakash comes with a plethora of other health benefits: Boosting your respiratory and brain functions functions, revving up your heart health and helping you look younger.

Packed with vitamin E and unsaturated fatty acids like omega-3 fats, include avocado in the form of salad or along with banana (mash one banana and one avocado) to attain its benefits. You can even use it in desserts.

Starting your day with a bowl of oats porridge or oats upma is a good idea, not only because it will fill you up but will boost your immunity and metabolism as well. Oats is rich in fibre and vitamin B12, which plays a key role in boosting immunity and lowering your risk of infections.

They are not only a perfect option to up your energy and satiate your hunger pangs, but also play a key role in strengthening your immunity. Eat 23 figs or walnuts in a day to increase your intake of potassium, zinc, iron and unsaturated fats, which improve your overall health. If you dont like nuts, make chikki or add them in oats or milk for effective results.

It is rich in probiotics, a kind of bacteria which fight infections. Including it in the diet not only aids in digestion but also improves immunity, lowering your risk of infections. Make sure you eat at least a small bowl of curd per day either in the form of buttermilk, raita or hung curd to boost immunity.

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Published : December 9, 2019 3:50 pm | Updated:December 9, 2019 5:40 pm

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Dont let diabetes take a toll on your immunity: Bolster it with natural remedies - TheHealthSite

The symbiotic relationship between host and microbes starts early in life and is important not only in terms of how the neonate microbiome ultimately develops, but also its potential impact on long-term infant health.

A current ongoing debate within the scientific community is whether gut colonization starts during pregnancy or at birth. Indeed, the crucial question of when bacteria first colonize the body has yet to be answered.

Microbial transfer at the feto-maternal interface

For long time, prevailing scientific dogma stated that neonates are born sterile and only upon delivery are they populated by microorganisms. For instance, in 1900, French pediatrician Henry Tissier declared: The fetus lies in a sterile environment.

Things changed in 1982, however, when a study found bacteria in the placenta. That discovery prompted scientists to accurately corroborate these findings.

By using both conventional culturing techniques and 16S ribosomal RNA gene and/or metagenomic sequencing in animal studies and humans in the mid-2000s, bacteria were also detected in what had been presumed to be sterile tissue from healthy term neonates. These included the placenta, amniotic fluid and meconium.

Contrary to initial belief, therefore, the evidence of bacterial presence in fetal membranes and in newborns first stool would not necessarily be a sign of infection. Furthermore, no distinction is made in this regard between premature infants and matched controls, which, in turn, might support the existence of a placenta microbiome in healthy pregnancies.

Other species such as clams, tsetse flies and turtles appear to inherit a mothers microbiome before birth. It is therefore no surprise that humans may also have microbes in utero.

Major caveats remain, however, making it difficult to prove the existence of a fetal-maternal microbiome. For instance, it is unclear which route microbes use to enter the intrauterine space, with their origin thought to be the mother. Furthermore, scientists leading this field remain uncertain about whether the organisms are viable or if free DNA is being detected, and it is unclear to what extent those bacteria are temporary passengers of the fetus or indeed residents in the fetal gut.

Contamination of the samples is also plausible. To tackle this issue, scientists have recently provided evidence of fetus exposure to bacterial DNAit remains unclear whether this originates from viable or dead bacteriaand metabolites prior to birth beyond the level of background contamination.

How the transfer of commensal organisms from the maternal gut to blood and systemic locations mechanistically occurs has been largely explored in mice, showing that maternal gut microorganisms migrate to various locations, including the mammary gland via an endogenous cellular route (called the bacterial entero-mammary pathway), taking place mainly during late pregnancy and lactation. These findings suggesting that transporting bacterial components from the gut to both blood and breast milk cells is possible, probably in the form of non-viable bacteria vectorized by immune cells, was formerly proposed from a study in mother-infant pairs. As such, this could program the neonatal immune system to better tackle the challenge of sorting out pathogens and commensal organisms.

There is also evidence of the impact on offspring development of symbiotic interactions between the mother and gut microbiome. In this regard, Elaine Hsiao and colleagues showed that injecting pregnant dams with a mock virus yielded offspring that exhibited autism-like symptoms. Such behavioral abnormalities in the offspring of maternal immune activation in mice were accompanied by defects in intestinal integrity and alterations in gut microbiota composition.

From an evolutionary perspective, it has been hypothesized that microbes may have influenced host sociability and behavior through the known microbiota-gut-brain axis as a way to propagate their own genetic material.

Other host-related and environmental factors such as maternal obesity and weight gain and exposure to environmental factors such as a high-fat diet and non-nutritive sweeteners may also affect infant microbial colonization and health programming later in life.

Thus, gut colonization during the perinatal period, especially during the first 2 to 3 years of life, is influenced by multiple biological and environmental factors and provides a window of opportunity to potentially reduce the risk of chronic diseases in childhood and later life.

Birth as the major microbial encounter

Although data exists regarding gut colonization before birth, some scientists remain skeptical and argue that the presence of bacterial DNA in presumably sterile fetal tissues such as the placenta does not lead to the establishment of the seed of the human microbiome before birth.

It is widely accepted that humans first exposure to microbes occurs in the birth canal. After delivery, maternal peripheral blood mononuclear cells and human breast milk cells contain the genetic material of a wide range of gut microbes, some of which are also found in infant feces.

At birth, newborn babies experience rapid colonization by microbes from their mothers and the surrounding environment. Delivery type is a critical factor involved in establishing the infant gut microbiota. Epidemiological studies indicated that cesarean section birth may come with a slightly increased risk of developing allergies and later obesity. Recent research has revealed that, compared with vaginal delivery, cesarean sections may predispose individuals to opportunistic infections.

Scientists have found no differences in the bacterial DNA recovered from placenta samples (of preterm infants and those of babies born at term) from that found on commercial reagents. Therefore, given that the placenta has a low bacterial biomass, it is also plausible that the bacterial DNA identified may derive from contamination through dust or commercial reagents.

More recently, an analysis of placental samples from more than 537 women, with either complicated or uncomplicated pregnancies, showed that the placenta was unlikely to be the major source of the infant microbiota. An experimental approach consisting of the use of two different kits for DNA extraction and different molecular methods to detect bacterial DNA allowed to reduce the chance of false-positive results due to contamination. The fact that almost 5% of placenta samples collected before labour contained group B Streptococci, a major cause of sepsis in newborns, also reveals that bacterial infection of the placenta is not a frequent cause of adverse pregnancy outcome.

Meanwhile, the observation of a handful of microbes in the placenta, umbilical cord blood, amniotic fluid and meconium does not necessarily support the existence of a complex microbiome, like the ones found in other niches such as the gut or saliva. As with the study of the breast milk microbiome, characterizing microorganisms colonizing the fetus prior to birth requires sophisticated methodologies that distinguish resident microbes from those that temporarily colonize the sample.

On the whole, it is clear that host interaction with intestinal microbes either during pregnancy or during the immediate postnatal period may have a profound impact on the neonatal microbiome and health and disease in later life by programming immune and metabolic pathways. Compensating for the lack of exposure to maternal microbes upon cesarean section delivery by a simple gesture might prove beneficial. Targeting the development of host-microbes symbiosis in early life might also be considered as a means of preventing the uncontrolled rise in incidence of chronic diseases that current medicine is not able to cure.

References:

Tissier H. Recherches sur la flore intestinale des nourrissons (etat normal et pathologique). G Carre and C Naud 1900;1-253.

Kovalovszki L, Villnyi Z, Pataki I, et al. Isolation of aerobic bacteria from the placenta. Acta Paediatr Acad Sci Hung. 1982; 23(3):357-60.

Aagaard K, Ma J, Antony KM, et al. The placenta harbors a unique microbiome. Sci Transl Med. 2014; 6(237):237ra65. doi: 10.1126/scitranslmed.3008599.

Collado MC, Rautava S, Aakko J, et al. Human gut colonisation may be initiated in utero by distinct communities in the placenta and amniotic fluid. Sci Rep. 2016; 6:23129. doi: 10.1038/srep23129.

Jimnez E, Marn ML, Martn R, et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008; 159(3):187-93. doi: 10.1016/j.resmic.2007.12.007.

Mshvildadze M, Neu J, Shuster J, et al. Intestinal microbial ecology in premature infants assessed using non-culture based techniques. J Pediatr. 2010; 156(1):20-5. doi: 10.1016/j.jpeds.2009.06.063.

Funkhouser LJ, Bordenstein SR. Mom knows best: the universality of maternal microbial transmission. PLoS Biol. 2013; 11(8):e1001631. doi: 10.1371/journal.pbio.1001631.

Stinson LF, Boyce MC, Payne MS, Keelan JA. The not-so-sterile womb: evidence that the human fetus is exposed to bacteria prior to birth. Front Microbiol. 2019; 10:1124. doi: 10.3389/fmicb.2019.01124.

Rodrguez JM. The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? Adv Nutr. 2014; 5(6):779-84. doi: 10.3945/an.114.007229.

Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013; 155(7):1451-63. doi: 10.1016/j.cell.2013.11.024.

Sherwin E, Bordenstein SR, Quinn JL, et al. Microbiota and the social brain. Science. 2019; 366(6465). doi: 10.1126/science.aar2016.

Garcia-Mantrana I, Collado MC. Obesity and overweight: impact on maternal and milk microbiome and their role for infant health and nutrition. Mol Nutr Food Res. 2016; 60(8):1865-75. doi: 10.1002/mnfr.201501018.

Wankhade UD, Zhong Y, Kang P, et al. Maternal high-fat diet programs offspring liver steatosis in a sexually dimorphic manner in association with changes in gut microbial ecology in mice. Sci Rep. 2018; 8:16502. doi:10.1038/s41598-018-34453-0.

Olivier-Van Stichelen S, Rother KI, Hanover JA. Maternal exposure to non-nutritive sweeteners impacts progenys metabolism and microbiome. Front Microbiol. 2019; 10:1360. doi: 10.3389/fmicb.2019.01360.

Rodrguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015; 26. doi: 10.3402/mehd.v26.26050.

Perez PF, Dor J, Leclerc M, et al. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics. 2007; 119(3):e724-32. doi: 10.1542/peds.2006-1649.

Shao Y, Forster SC, Tsaliki E, et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature. 2019; 574(7776):117-21. doi: 10.1038/s41586-019-1560-1.

Lauder AP, Roche AM, Sherrill-Mix S, et al. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome. 2016; 4(1):29. doi: 10.1186/s40168-016-0172-3.

de Goffau MC, Lager S, Sovio U, et al. Human placenta has no microbiome but can contain potential pathogens. Nature. 2019; 572(7769):329-34. doi: 10.1038/s41586-019-1451-5.

Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016; 22(3):250-3. doi: 10.1038/nm.4039.

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When do bacteria first colonize the body? How host-microbe symbiosis is established in early life and its impact on neonatal health - Gut Microbiota...

1st December is World AIDS Day which raises awareness of HIV and AIDS around the world. There have been huge leaps in the treatment of HIV and AIDS in recent years but its still important to raise awareness and support people to live well with HIV.

To mark World AIDS Day 2019 there are a number of initiatives happening around the world. The Terrence Higgins Trust is campaigning to end HIV transmissions in the UK by 2030. The National AIDS Trust is encouraging people to Rock the Ribbon Together and wear their red ribbon to take the isolation out of HIV, show support for people living with HIV and commemorate those who have died from an AIDS-related illness. The World Health Organization and UNAIDS are recognising the essential role of communities in the AIDS response at international, national and local levels.

What are HIV and AIDS?

Human immunodeficiency virus (HIV) affects the bodys immune system and damages the cells. The virus continues to affect the immune system which leads to immunodeficiency. This makes people with HIV more susceptible to infection and disease as the immune system cannot fight them.

Acquired immunodeficiency syndrome (AIDS) is the collection of illnesses, symptoms or infec-tions that can affect the individual when their immune system has been severely affected by HIV. These can be life-threatening.

MSD has been at the forefront of several break throughs in the HIV field

Symptoms and infection

If people are not receiving effective treatment, HIV can be transmitted via some body fluids, including through condomless sex, blood transfusion, contaminated needles, and vertical transmission (from mother to baby during pregnancy or through breastfeeding.)

People may not be aware that they have acquired HIV because they may only experience flu-like symptoms. This is called a seroconversion illness and common symptoms include sore throat, fever and a rash.

According to the Terrence Higgins Trust (THT), seroconversion is a sign that the immune system is reacting to the presence of the virus in the body. Its also the point at which the body produces antibodies to HIV. Once seroconversion has happened, an HIV test will detect antibodies and give a positive result.

Seroconversion illness happens to most (but not all) people shortly after infection. It can be severe enough to put someone in hospital, or so mild that its mistaken for something like flu although a blocked or runny nose is not usually a symptom.

If a person has recently acquired HIV and has not been diagnosed and started treatment, some of their body fluids (eg blood, seminal fluid, vaginal fluid) can be infectious in the early weeks and months after transmission. However, once a person has been diagnosed and is on effective treat-ment, their viral load becomes undetectable, which means they cannot pass on HIV. It can take up to six months from starting treatment to becoming undetectable, but many patients achieve an unde-tectable viral load much sooner than that.

Developments with treatments

There are more than 25 anti-HIV drugs, divided into six classes. Each class works against HIV in a specific way with most people on a fixed dose combination pill. THT classes these as:

Antiretroviral therapy

Antiretroviral therapy (ART) is medication which stops the virus from reproducing in the body. It can reduce the amount of virus in the blood to undetectable levels meaning it cannot be passed on. It is recommended that people start antiretroviral treatment as soon as they are diagnosed with HIV.

PrEP

PrEP, or pre-exposure prophylaxis, is a drug taken by HIV-negative people to reduce the risk of getting HIV. PrEP is a two NRTIs combination drug, which blocks HIV and considerably reduces the risk of transmission. PrEP is taken either on a daily basis or as event-based therapy (on the days before, of, and after condomless sex). However, dosing recommendations will depend upon the type of sex (anal or vaginal). There is currently a PrEP IMPACT Trial taking place in England until the end of 2019, which is recruiting 26,000 participants who are at high risk of HIV. The trial is to assess the need for PrEP in England, not the effectiveness of PrEP, which has already been established in earlier trials.

RIVER study

The RIVER study was a clinical trial designed to wake up and then kill the HIV virus in people in whom it was controlled by antiretroviral treatment, in the hope that by doing so, researchers would be able to cure HIV by completely eradicating the virus from the body. The RIVER study ran from 2015 to 2018 and was led by investigators from Imperial College London, the University of Oxford, MRC Clinical Trials Unit at UCL, and the University of Cambridge.

On publication of initial findings, RIVER Chief Investigator, Professor Sarah Fidler of Imperial College London, said: In the RIVER study, we found that all the separate parts of the kick and kill approach worked as expected and were safebut the study has shown that this particular set of treatments together didnt add up to a potential cure for HIV, based on what weve seen so far.

Remission

There have been two confirmed cases of HIV remission reported. The first case, the Berlin Patient received a stem cell transplant from a donor to treat leukaemia. The donor had two copies of the CCR5 32 allele, a genetic mutation that prevents expression of an HIV receptor CCR5.

In March 2019, news was released that HIV remission had been achieved in a second person. The case, published in Nature and carried out by scientists at University College London, Imperial Col-lege London, the University of Cambridge and the University of Oxford, said a second person had experienced sustained remission from HIV-1 after ceasing treatment. The male patient was diag-nosed with HIV infection in 2003 and had been on antiretroviral therapy since 2012. Later in 2012, he was diagnosed with advanced Hodgkins Lymphoma. In addition to chemotherapy, he under-went a haematopoietic stem cell transplant from a donor with two copies of the CCR5 J32 allele in 2016.

Despite these two cases, researchers say the treatment is not considered appropriate due to the tox-icity of chemotherapy. However, understanding the mechanisms behind these cases may lead to a potential cure in the future.

HIV treatment has progressed significantly in recent years meaning that people living with HIV and receiving appropriate treatment can expect a normal life expectancy

Becoming undetectable

An important breakthrough in HIV research looks at transmission from an HIV positive person to an HIV negative partner. Two studies, PARTNER 1 published in July 2016, and PARTNER 2 published in 2018 and reported in the Lancet in May 2019, both report zero HIV transmissions from a positive partner on ART to their negative partner through sex without using a condom. In PARTNER 1, this was after nearly 900 couples, both heterosexual and gay, had sex more than 58,500 times without using condoms, and in PARTNER 2 almost 800 gay couples had sex more than 77,000 times without using condoms.

Together, these studies contributed to the evidence that led to Undetectable = Untransmittable and support U=U. This means there is zero risk of transmitting HIV when viral load is undetectable.

The 90-90-90 UNAIDS targets call for 90% of those living with HIV to be diagnosed, 90% to be on treatment and 90% of those treated to have an undetectable viral load.

By November 2018, public health data suggested that the UK was doing well against these targets with 92% diagnosed, 98% on treatment and 97% having an undetectable viral load.THTs Cant Pass It On campaign to end HIV transmission altogether and end stigma about the virus, is raising awareness of the facts around HIV and effective treatment, communicating that someone living with HIV and on effective treatment cant pass it on.

MSDs work in HIV

MSD has been at the forefront of several breakthroughs in the HIV field including being the first to publish the crystal structure of HIV protease. New scientific innovation remains crucial but beyond this, MSD continues to stand alongside the global community of people living with HIV. Living well with HIV starts with a person knowing their status and accessing effective treatment, but the needs of the HIV community go well beyond this.

In the UK, MSD continues to partner with the community to tackle stigma and inequalities and help put people at the centre of their own care. The Whole Person Care Partnership is a group of lead-ing HIV organisations which have worked with MSD to establish the importance of sound public policy in these areas.

Anyone whose HIV is undetectable in the blood cannot pass on the virus sexually. This concept is known as Undetectable Equals Untransmittable or U=U. MSD recently collaborated with its Whole Person Care partners in a U=U social media campaign, reaching more than half a million people. The campaign draws links between U=U and stigma, self- management, care planning and inequalities. Such initiatives are just a start and the short films making up the campaign can be found on the MSD-in-the-UK YouTube channel. The aim for everyone involved in the HIV field is to make living well with HIV a reality, one day, for everyone.

The future

HIV treatment has progressed significantly in recent years meaning that people living with HIV and receiving appropriate treatment can expect a normal life expectancy. Work still needs to be done but organisations from the pharmaceutical industry to THT and the World Health Organiza-tion are working hard to change the landscape.

With thanks to British HIV Association and Terrence Higgins Trust

Go to http://www.bhiva.org and http://www.tht.org.uk

Sources:

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Living well with HIV and AIDS around the world - Pharmafield

MB-107 preceded by low-dose busulfan conditioning continues to be well tolerated and results in development of functional immune system in newly diagnosed infants with XSCID

Enhanced transduction procedure is demonstrating improvements in older patients with XSCID who received prior hematopoietic stem cell transplantation

Data presented by St. Jude Childrens Research Hospital and National Institutes of Health at 61st American Society of Hematology Annual Meeting

NEW YORK, Dec. 09, 2019 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, announced today that updated Phase 1/2 clinical data for MB-107 lentiviral gene therapy for X-linked severe combined immunodeficiency (XSCID) were presented on Saturday by St. Jude Childrens Research Hospital (St. Jude) and today by the National Institutes of Health at the 61st American Society of Hematology (ASH) Annual Meeting.

MB-107 is currently being assessed in two Phase 1/2 clinical trials for XSCID: the first in newly diagnosed infants under the age of two at St. Jude, and the second in patients over the age of two who have received prior hematopoietic stem cell transplantation at the National Institutes of Health. Under a licensing partnership with St. Jude, Mustang intends to develop the lentiviral gene therapy for commercial use as MB-107. The U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to MB-107 for the treatment of XSCID in August 2019.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, The updated clinical data presented at the 2019 ASH Annual Meeting underscore the curative potential of MB-107 for newly diagnosed infants with XSCID, as well as its meaningful impact on older XSCID patients who received prior hematopoietic stem cell transplantation. St. Jude recently received the 2019 Smithsonian Magazine American Ingenuity Award for development of the lentiviral gene therapy, highlighting its potential to have an impact on this devastating disease. We are excited to be working with St. Jude and NIH to advance MB-107 and look forward to transferring the IND from St. Jude to Mustang in the first quarter of 2020.

Lentiviral Gene Therapy with Low Dose Busulfan for Infants with X-SCID Results in the Development of a Functional Normal Immune System: Interim Results of an Ongoing Phase I/II Clinical Study (Abstract Number: 2058)Poster presentation: Ewelina Mamcarz, M.D., Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Childrens Research Hospital, Memphis, TN, USA

Interim data from the multicenter Phase 1/2 clinical trial for infants under the age of two treated with the lentiviral gene therapy preceded by low exposure-targeted busulfan conditioning were published in the New England Journal of Medicine. Updated data presented at the 2019 ASH Annual Meeting include three more patients (n=11), 8 months additional median follow up (23.6 months; range: 1.5 to 33.9 months), more extensive analysis of T and B cell functional recovery, and detailed vector integration site studies.

Data Highlights:

The results from treatment with low-dose busulfan conditioning and the novel lentiviral gene therapy in newly diagnosed infants with XSCID continue to be very promising, said Dr. Mamcarz. We are pleased that the therapy has been well tolerated and all patients with a follow up of more than 3 months recovered from pre-existing infections, are off protective isolation and prophylactic antimicrobials, and have normal growth in respect to height and weight. This reinforces our belief that the lentiviral gene therapy has the potential to be an attractive alternative to current XSCID therapies.

Enhanced Transduction Lentivector Gene Therapy for Treatment of Older Patients with X-Linked Severe Combined Immunodeficiency (Abstract Number: 608)Oral presentation: Harry Malech, M.D., Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA

Early outcome data for five older children and young adults with XSCID who received the lentivector (also known as lentiviral) gene therapy as salvage therapy after having previously received haplo-identical hematopoietic stem cell transplantation (HSCT) as infants without chemotherapy-based conditioning were previously reported and published in Science Translational Medicine. By 2016, three additional patients were treated, and the cohort of eight patients (referred to as Cohort A) has now been followed for 3 to 7 years. Among Cohort A, gradual clinical benefit in the clearance of chronic norovirus and associated improved abdominal complaints, malabsorption, growth and IgG production were observed, and four patients were able to cease immunoglobulin replacement therapy.

While the results were positive, the relatively inefficient transduction of hematopoietic stem/progenitor cells (HSPCs) required large quantities of vector. This resulted in relatively low VCN in myeloid cells in some patients, with delayed immune cell recovery and persistent clinical disease, especially in the last patient treated (patient 8). To address this, NIH developed a refined enhanced transduction (ET) procedure consisting of a single overnight transduction after 48 hours pre-stimulation in cytokines (Stem cell factor, Thrombopoietin, Flt3-ligand; 100ng/mL) and incorporated transduction enhancers LentiBoost 1:100 and dimethyl prostaglandin 2 (dmPGE2; 1uM).

The presentation at the 2019 ASH Annual Meeting included data from six patients (referred to as Cohort B) treated by NIH, including re-treatment of patient 8. The patients, who were aged 12 to 36, had significant problems with donor T cell infiltration of liver, bone marrow and kidneys, and were nearly absent of B and NK cells. The enhanced transduction procedure achieved much greater transduction efficiencies than were observed in Cohort A, with greater than 10-fold less vector, and resulted in faster immune reconstitution and more significant clinical benefit by 3 months.

We are encouraged by the significantly improved measures of early clinical outcomes from lentivector gene therapy in older children and young adults with XSCID using an enhanced transduction procedure with the addition of LentiBoost and dmPGE2, said Dr. Malech. Notably, we have seen an early appearance of B and NK cells at much higher levels in Cohort B than we previously observed in Cohort A, even at years after treatment. We look forward to continuing to closely monitor patients and report outcomes.

About Mustang BioMustang Bio, Inc. (Mustang) is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T and CRISPR/Cas9-enhanced CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for XSCID. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission. Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Company Contacts:Jaclyn Jaffe and William BegienMustang Bio, Inc.(781) 652-4500ir@mustangbio.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 430-7576daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

Excerpt from:
Mustang Bio Announces Updated Clinical Data on MB-107 Lentiviral Gene Therapy for Patients with X-Linked Severe Combined Immunodeficiency -...

DetailsCategory: VaccinesPublished on Monday, 09 December 2019 10:31Hits: 95

BASEL, Switzerland I December 9, 2019 I Nouscom, an immuno-oncology company developing off-the-shelf and personalized cancer neoantigen vaccines, announced today that the first patient has been dosed in a Phase 1 clinical trial evaluating its lead candidate, NOUS-209. In this first-in-human trial NOUS-209, an off-the-shelf therapeutic vaccine based on shared tumor neoantigens, is being administered to patients with Microsatellite Instable High (MSI-H) gastric, colorectal and gastro-esophageal junction cancers (tumors characterized by a defective DNA mismatch repair system) in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab.

NOUS-209-01 (NCT04041310) is a US multicenter Phase 1 open-label, dose-escalation study, assessing the safety and tolerability of the NOUS-209 vaccine in combination with pembrolizumab to determine the recommended Phase 2 dose. The study will evaluate vaccine-induced immune responses, as well as preliminary signs of anti-tumor activity in enrolled patients. Based on preclinical data, NOUS-209 is expected to induce potent and broad CD8+ and CD4+ responses in humans. Initial clinical data are expected in 2020.

Dr. Michael J. Overman, Principal Investigator of the trial and Professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, explained: "We have seen tremendous change in our approach to MSI-high metastatic solid tumors over the last few years, but the majority of patients do not respond to single agent immunotherapy. Hence, further optimization of our approach for MSI-high cancers is needed. Agents like NOUS-209 that stimulate the patient's immune response and direct it specifically against the cancer cells reflect a tremendous scientific evolution in our understanding of these cancers and represents an extremely promising approach for these cancers."

Dr. Elisa Scarselli, Chief Scientific Officer and Co-Founder of Nouscom, said "This first-in-human trial evaluating NOUS-209 in combination with pembrolizumab is a significant milestone for Nouscom. NOUS-209 leverages a core strength of the company's platform, namely the capacity of its proprietary viral vectors to encode a large number of neoantigens. NOUS-209 was named because it comprises 209 shared Frame Shift Peptides (FSPs) selected using a proprietary algorithm. This feature of NOUS-209 enables it to be developed as an off-the-shelf neoantigen vaccine that does not require patient screening prior to treatment. Furthermore, it is designed to have broad coverage across the MSI patient population by targeting multiple neoantigens in each patient, and as such is expected to address tumor heterogeneity.We look forward to the initial clinical data in 2020."

About Nouscom

Nouscom is a privately held oncology company developing next-generation immunotherapies. Nouscom's proprietary technology platform harnesses the full power of the immune response by combining viral vectored genetic vaccines based on neoantigens with other immunomodulators.

Nouscom is currently advancing the development of its lead program, NOUS-209, an off-the-shelf cancer vaccine based on shared frame shift neoantigens, into clinical studies. The Company will also continue to develop its product candidate, NOUS-PEV, a personalized cancer neoantigen- vaccine, which is expected to enter clinical studies in 2020.

Nouscom is led by an experienced management team that has worked together for many years in previous successful enterprises, including Merck, Novartis, and Okairos (acquired by GSK), and are veterans in the field of viral vectored genetic vaccines.

Nouscom, which was founded in 2015 and is headquartered in Basel, Switzerland with operations in Rome, Italy, is backed by international life sciences investors: 5AM, Abingworth, LSP (Life Sciences Partners) and Versant Ventures.

For more information on Nouscom, please visit the company's website at http://www.nouscom.com.

SOURCE: Nouscom

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Nouscom - First Patient Dosed in a Phase 1 Trial With NOUS-209, an 'off-the-shelf' Neoantigen Cancer Vaccine, in MSI-High Solid Tumors | Vaccines |...

Worldwide more than 140,000 people died from measles in 2018, according to new estimates from the World Health Organization (WHO) and the United States Centers for Diseases Control and Prevention (CDC). These deaths occurred as measles cases surged globally, amidst devastating outbreaks in all regions.

Most deaths were among children under 5 years of age. Babies and very young children are at greatest risk from measles infections, with potential complications including pneumonia and encephalitis (a swelling of the brain), as well as lifelong disability - permanent brain damage, blindness or hearing loss.

Recently published evidence shows that contracting the measles virus can have further long-term health impacts, with the virus damaging the immune systems memory for months or even years following infection. This immune amnesia leaves survivors vulnerable to other potentially deadly diseases, like influenza or severe diarrhoea, by harming the bodys immune defenses.

The fact that any child dies from a vaccine-preventable disease like measles is frankly an outrage and a collective failure to protect the worlds most vulnerable children, said Dr Tedros Adhanom Ghebreysus, Director-General of the World Health Organization. To save lives, we must ensure everyone can benefit from vaccines - which means investing in immunization and quality health care as a right for all.

Measles is preventable through vaccination. However, vaccination rates globally have stagnated for almost a decade. WHO and UNICEF estimate that 86% of children globally received the first dose of measles vaccine through their countrys routine vaccination services in 2018, and fewer than 70% received the second recommended dose.

Worldwide, coverage with measles vaccine is not adequate to prevent outbreaks. WHO recommends that 95% vaccination coverage with two doses of measles vaccine is needed in each country and all communities to protect populations from the disease.

Estimating the total number of cases and deaths globally and by region, the report finds that the worst impacts of measles were in sub-Saharan Africa, where many children have persistently missed out on vaccination.

In 2018, the most affected countries - the countries with the highest incidence rate of the disease - were Democratic Republic of the Congo (DRC), Liberia, Madagascar, Somalia and Ukraine. These five countries accounted for almost half of all measles cases worldwide.

Weve had a safe and effective measles vaccine for over 50 years, said Dr. Robert Linkins, Branch Chief of Accelerated Disease Control and Vaccine Preventable Disease Surveillance at the CDC and Chair of the Measles & Rubella Initiative. These estimates remind us that every child, everywhere needs and deserves - this life-saving vaccine. We must turn this trend around and stop these preventable deaths by improving measles vaccine access and coverage.

While the greatest impacts have been in the poorest countries, some wealthier countries have also been battling measles outbreaks, with significant ramifications for peoples health.

This year, the United States reported its highest number of cases in 25 years, while four countries in Europe - Albania, Czechia, Greece and the United Kingdom lost their measles elimination status in 2018 following protracted outbreaks of the disease. This happens if measles re-enters a country after it has been declared eliminated, and if transmission is sustained continuously in the country for more than a year.

The Measles & Rubella Initiative (M&RI) which includes the American Red Cross, CDC, UNICEF, the United Nations Foundation and WHO as well as Gavi, the Vaccine Alliance, are helping countries respond to measles outbreaks, such as through emergency vaccination campaigns.

In addition to rapidly immunizing against measles, outbreak response also includes efforts to reduce the risk of death through timely treatment, especially for related complications like pneumonia. With partners, WHO is therefore providing support to help countries manage cases, including training health workers in effective care for children suffering the effects of the disease.

Beyond outbreak response, there is an urgent need for countries and the global health community to continue investing in high quality national immunization programmes and disease surveillance, which helps ensure measles outbreaks are rapidly detected and stopped before lives are lost.

It is a tragedy that the world is seeing a rapid increase in cases and deaths from a disease that is easily preventable with a vaccine, said Dr Seth Berkley, CEO of Gavi, the Vaccine Alliance. While hesitancy and complacency are challenges to overcome, the largest measles outbreaks have hit countries with weak routine immunization and health systems. We must do better at reaching the most vulnerable, and that will be a fundamental focus of Gavis next five-year period.

Over the last 18 years, measles vaccination alone is estimated to have saved more than 23 million lives.

M&RI is a global partnership founded by the American Red Cross, the CDC, the United Nations Foundation, UNICEF and WHO, that is committed to achieving and maintaining a world without measles, rubella and congenital rubella syndrome. Founded in 2001, the Initiative has helped vaccinate over 2.9 billion children and save over 21 million lives by increasing vaccination coverage, improving disease response, monitoring and evaluation, and building public confidence and demand for immunization.

We are alarmed at the increase in measles in the US and around the globebut there is hope, said Gail McGovern, President & CEO, American Red Cross. Measles outbreaks are entirely preventable through strong systems that ensure no child misses lifesaving vaccines.

The unacceptable number of children killed last year by a wholly preventable disease is proof that measles anywhere is a threat to children everywhere, said Henrietta Fore, UNICEFs Executive Director. When children go unvaccinated in significant numbers, entire communities are at risk. We see that eventoday in remote places like in the Democratic Republic of the Congo,where measles has killed more than 4,500 children under the age of five so far this year; or in Samoa, where a rapidly spreading measles outbreak has left many children ill and unable to go to school.

This latest data show that we are unfortunately backsliding in our progress against an easily-preventable disease: measles, said Kathy Calvin, President and CEO of the United Nations Foundation. But we can turn the tide against these outbreaks through collective action, robust political commitment, and closing critical funding gaps. Working together worksits the only way we will be able to reach everyone, everywhere with life-saving vaccines and services and, more broadly, reach the UNs Sustainable Development Goals.

Progress Toward Regional Measles Elimination Worldwide, 20002017 is a joint publication of WHO and CDC. It is published within the WHO Weekly Epidemiological Record and in CDCs Morbidity and Mortality Weekly Report.

Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographical area for more than 12 months. Conversely, a country is no longer considered to be measles free if the virus returns and transmission is sustained continuously for more than a year.

These estimates are the result of statistical modeling undertaken by WHO. Each year, the model is adjusted for the entire time series from 2000 to the current year. This years modelling shows that there were 9,769,400 estimated measles cases and 142,300 related deaths globally in 2018, decreasing from 28,219,100 cases and 535,600 deaths in 2000. In 2017, there were 7,585,900 estimated cases and 124,000 estimated deaths.

By region in 2018, WHO estimates that in the African region, there were 1,759,000 total cases and 52,600 deaths; in the Region of the Americas, 83,500 cases; in the Eastern Mediterranean Region, 2,852,700 cases and 49,000 deaths; in the European region, 861,800 cases and 200 deaths; in Southeast Asia, 3,803,800 cases and 39,100 deaths; and in the Western Pacific, 408,400 cases and 1300 deaths.

While estimates provide a useful indication of measles impacts and longer-term trends, reported cases provide real-time insights and comparisons. There were a total of 353,236 cases reported to WHO in 2018. In 2019, as of mid-November, there had already been over 413,000 cases reported globally, with an additional 250,000 cases in DRC (as reported through their national system); together, this marks a three-fold increase compared with this same time in 2018.

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More than 140,000 die from measles as cases surge worldwide - World Health Organization

Chimeric antigen receptor (CAR) T-cell therapy targeting both BCMA and CD38 induced promising responses among patients with multiple myeloma who had been treated with at least 3 prior therapies and whose disease had spread outside of the bone marrow, supporting further exploration of the dual-targeted therapy, according to Yu Hu, MD, PhD.

This is the first clinical trial of anti-BCMA and CD38 dual-targeted CAR T-cell therapy in refractory multiple myeloma. Our study demonstrates improved efficacy and manageable safety, Hu, of Union Hospital at Huazhong University of Science and Technology in Wuhan, China, said during a presentation to an audience at the 61st Annual American Society of Hematology Annual Meeting and Exposition.

The objective response rate was 90.1%, with 12 patients achieving a stringent complete response (sCR) as their best response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a partial response (PR), meaning that the level of M-protein in the blood or urine was reduced but still detectable, with 2 achieving a very good partial response (VGPR). One patient had a minor response. Eighteen patients (81.8%) reached bone marrow minimal residual diseasenegative status.

At the cutoff date of October 31, 2019, 19 patients were still alive with 10 still in sCR, 1 with VGPR, 4 with PRs. Three patients experienced relapse and 1 patient had progressive disease.

The median progression-free survival (PFS) had not been reached with a PFS rate at 9 months of 78.9%. For 17 patients remaining in remission at 7 months after treatment, median duration of response was 28.8 weeks.

Cytokine release syndrome (CRS) was observed in 20 out of 22 patients (90.9%), with 11 having grade 1 CRS and 4 with grade 2. Severe CRS grade 3 occurred in 5 (22.7%) and only 6 patients overall required treatment. No neurotoxicity was observed. Hepatotoxicity was seen in 3 patients (13.6%) and 1 patient experienced nephrotoxicity.

The peak time of CAR T cells in peripheral blood occurred from day 7 to day 15 after infusions in patients who achieved sCR and from day 14 to day 30 in patients without sCR. The longest duration of CAR T cells in the peripheral blood was >450 days. BM38 CAR was tested by quantitative polymerase chain reaction (qPCR) in the peripheral blood.

Eight out of 9 patients achieved complete or partial response of extramedullary disease, meaning these tumors were undetectable by CT scan.

With this dual-targeted CAR T-cell therapy, we have demonstrated a high response rate, especially a higher rate and longer duration of stringent complete response, compared with other therapies, as well as effective elimination of extramedullary lesions, with no serious neurologic adverse effects and manageable levels of other adverse effects, Hu said.

Among patients with multiple myeloma, roughly 10% will develop tumors in their organs or soft tissue known as extramedullary tumors. Patients who develop these often have poor responses to available therapies, experience a decrease in their quality of life, and have poor prognoses. According to Hu, patients treated in the study demonstrated that the novel dual-targeting CAR T-cell therapy may effectively eliminate extramedullary tumors.

This new CAR T cell [therapy] may have effects on the suppressor B cell. That means you can overcome the immunosuppression of the tumor environment, Hu said.

In total, 22 patients with a median age of 59 year (range, 49-72), half of whom were male, were treated in the dose-climbing phase I trial. All patients had multiple myeloma that had returned or not responded to at least 3 prior therapies. Nine patients (41%) had extramedullary tumors. Myeloma cells in the bone marrow were observed at a median of 9.7% (0.50%-56.1%) by flow cytometry. Seventy-three percent of patients had cytogenetic abnormalities such as 1q21 amp (54.6%) and deletion of chromosome 13q (40.9%).

All patients were treated with a 3-day chemotherapy regimen of fludarabine at 25 mg/m2 and cyclophosphamide 250 mg/m2 to make room in the immune system for engineered CAR T cells before infusion with the product. Patients were infused with CAR T cells at 0.5 106/kg to 4.0 106/kg with at least 2 patients treated at every dose level.

Investigators plan to continue follow up on these patients for 2 years. A phase II trial is being planned in both China and the United States to test the treatments efficacy in a larger number of patients.

Reference:

Mei H, Hu Y, Li C, et al. A bispecific CAR-T cell therapy targeting BCMA and CD38 for relapsed/refractory multiple myeloma: updated results from a phase 1 dose-climbing trial. Presented at: 61st Annual American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 930. https://bit.ly/38imXXG.

This article originally appeared on OncLive, titled Extramedullary Multiple Myeloma Responds to Dual-Targeting CAR T-Cell Therapy.

Link:
Promising Responses from Dual-Targeting CAR T-Cell Therapy in Myeloma Support Further Exploration - Cancer Network

There's more to this trusty festive staple thank you might think, writes Fiann Nuallin.

The only time some people partake of Brussels sprouts is in a festive scenario. Well there is much more to sprouts (Brassica oleracea, from Gemmifera group of cabbages) than the tradition of dressing the plate beside the stuffing.

Packed with antioxidants and dietary fibre they serve to mop up a lot of the junk we indulge in at this time of the year but also are worth becoming a regular in the five-a-day rota during the rest of the year.

I say the rest of the year as they freeze beautifully but in terms of fresh seasonality they are in the main, a winter crop with a season than starts in October and ends in March. Garden-grown varieties can be set up to begin producing from mid-August.

There are early and late cultivars but generally the tradition is, for early harvests to sow under cover or in a cold frame in February or March. Otherwise sow or plant plugs from late April/early May.

Pick a sheltered, sunny site, to grow on.

The sprouts are little fibre bullets supporting intestinal health and helping to lower blood sugars and high lipid accumulations from triglycerides to cholesterol. Dietary fibre is of prime importance to anyone dealing with diabetes, high cholesterol and digestive conditions.

The fibre and the stomach-strengthening phytochemistry of sprouts have seen them included in dietsto support Crohns disease, irritable bowel syndrome, and ulcerative colitis.

Brussels sprouts contain an antibacterial agent known as glucoraphanin which protectsthe stomach from bacterial overgrowth particularly good in fighting off candida and Helicobacter pylori.

They are often though of as a detox or system cleanse vegetable.

The richness of their glucosinolates have been studied as valid triggers to the detoxification and clearance of cancer-causing substances. Those sulphur-rich molecules also drive a better immune system.

The boost to the whole system is derived from the amazing quality of Brussels sprouts antioxidants.

Packed with vitamin C and beta-carotene to mop up free radical damage and protect our DNA and cellular health but also filled with fabulous flavonoid such as caffeic acid, ferulic acid, isorhamnetin, quercitin, and kaempferol all not just limiting the ageing process but working to disarm allergies and inflammation.

Brusssels sprouts are one of the bestanti-inflammatory vegetables, in part due to the high vitamin K content which regulates inflammatory responses but also via thede-inflaming action of glucosinolates one in particular glucobrassicin has shown effective in limiting rheumatoid arthritis flare-ups.

The glucobrassicin molecule converts into isothiocyanate which may be helpful in improving insulin resistance by lessening inflammation that complicates diabetes.

Sprouts contain zea-xanthin known as an eye health carotenoid beneficial to prevent age-related macular degeneration and bolster eyesight in general, those 20/20 rabbits eat more than carrots.

Sprouts also supply omega-3 fatty acids, and one of them is alpha-linolenic acid which is of benefit to the cardiovascular system and support the nervous system.

Ala is also known to lower inflammation, blood pressure and cholesterol levels.

When it comes to diets for cancer prevention and recovery, glucosinolates in cruciferous vegetables often hit the headlines. Of all the crucifers, Brussels sprouts contain the most and easily activated levels of sulforaphanes and isothiocyanates known to offer protection from colonic, prostate and endometrial cancers.

These same agents are helpful in battling viral and bacterial infections that can affect us across winter months. The trick is to leave enough sprout phytochemistry intact to do the job most effectively and thats down to how you cook.

In recent years, perhaps as a drive to boost flagging sales, the odd celebrity chef appears with a roasted sprout and chestnut dish or a roasted honey-glazed sprout.

Great and tasty but to get the best from sprouts, steam them. Years of boiling to a sulphurous sog has put many off. If you smell the cabbage aroma you have overcooked the sprout. Steaming is fast and less aromatic.

Steaming also keeps those healthy phytochemicals more integral and ready to be absorbed upon eating.

A 4-6-minute steam will do the trick. As some of the sprouts chemistry is enzymatically released, it is a good idea to slice in half or quarter and allow the chopped parts to sit for five minutes before cooking. This action lets the enzymes at the cuts do their thing.

Abacus is an easy-to-grow early tomid-season cropper. Good solid sprouts.

Bosworth is an easy-to-grow late cropper best yields after Christmas into spring.

Brigitte F1 is a favourite among Irish growers quite nutty in flavour but also a long season and disease resistance.

Crispus F1 is a mid-season, clubroot-resistant variety. Small, tight sprouts.

Chronos is a clubroot-resistant variety, grown as a mid-season.

Diablo is a mid-to-late-season cropper. Dark green sprouts.

Evesham Special is a shorter growing but long and prolific harvester from September on.

Maximus is one of the early to mid-season croppers. Plenty of mid- to dark- green sprouts.

Red Bull Also known as red ball, it yields attractive and tasty dark red sprouts.

Revenge is known as a late variety and can still be vigorous and prolific in spring.

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Why sprouts earn a place on your plate all year round - Irish Examiner

Abstract

IFN- produced by T cells directly induces intestinal stem cell death upon inflammation-induced intestinal injury (see the related Research Article by Takashima et al.).

Intestinal regeneration upon tissue damage is fueled by intestinal stem cells (ISCs) residing in the crypt bottom of the epithelium and marked by the gene Lgr5 (1, 2). There is growing evidence that tissue repair is at least partially mediated by a regenerative inflammatory response (3, 4). How inflammation-induced intestinal injury influences ISCs and their microenvironment (stem cell niche) remains poorly understood. In this issue of Science Immunology, Takashima et al. (5) explore the changes in the ISC niche in vivo upon T cellmediated injury as a model of graft-versus-host disease (GVHD) and in vitro using organoid T cell cocultures. Although earlier studies already implicated interferon- (IFN-) as a negative regulator of intestinal epithelial homeostasis (68), Takashima et al. now demonstrate that IFN- directly acts on ISCs by triggering apoptosis.

In an allogeneic bone marrow transplant (BMT) model, Takashima and colleagues found that ISC numbers per intestinal crypt were markedly reduced in mice receiving bone marrow alone or bone marrow and T cells when compared with normal control mice. While the ISCs in the mice receiving only bone marrow recovered 7 days later, the ISC numbers remained reduced in those mice also transplanted with donor T cells. Of note, Paneth cell numbers were also reduced after ISC depletion. The numbers of organoids established from the intestines of mice 10 days after BMT recovered back to that of control mice, whereas the organoid forming capacity from crypts of mice after combined transplantation of bone marrow and T cells remained significantly lower. Similar in vivo and in vitro results were obtained when autoreactive T cells were transplanted, pointing to a common feature of T cellmediated intestinal injury.

As seen by three-dimensional confocal microscopy, intraepithelial T cells (CD3+ IELs) preferentially localized to the villus region, whereas lamina propriaassociated T cells (CD3+ LPLs) were equally distributed along the crypt-villus axis of control mice (Fig. 1A). Conversely, mice receiving bone marrow and allogeneic T cells showed a progressive increase in the density of both CD3+ LPLs and CD3+ IELs in the crypt region.

To identify signaling molecules that cause the loss of ISCs in this model, Takashima and colleagues performed several elegant murine and human epithelial organoid coculture experiments. Murine nave allogeneic T cells did not impair murine intestinal organoid numbers, whereas alloreactive T cells effectively reduced organoid numbers. Likewise, human allogeneic cytotoxic T cells robustly inhibited human intestinal organoid forming efficiency. Even bead-activated autologous T cells suppressed human intestinal organoid growth. The authors then proceeded to screen for potential pathways mediating cytotoxicity. Organoids cocultured with T cells in the presence of antiIFN- neutralizing antibodies showed normal growth. Although IFN- receptor (IFN-R)depleted T cells were still able to affect organoid viability, IFN-Rdepleted organoids were resistant to T cellmediated killing. Organoid toxicity by IFN- was also observed in the absence of T cells. Live imaging confirmed the progressive ISC depletion upon organoid exposure to IFN-. Treatment of organoids with the immunosuppressive JAK1/2 inhibitor ruxolitinib robustly preserved numbers of both organoids and ISCs in the presence of IFN-, irrespective of whether the organoids were cultured alone or together with T cells. The authors additionally demonstrated that JAK1-depleted organoids are resistant to IFN- treatment. Further downstream, ruxolitinib prevented STAT1 phosphorylation by IFN- in intestinal crypts, and, in line, STAT1-depleted organoids were resistant to growth suppression in response to IFN- treatment.

IFN-treated organoids showed reduced expression of ISC marker genes. ISCs underwent apoptosis in vitro in a direct response to IFN-. Next, the authors confirmed in vivo that ISC numbers did not change upon transplanting allogeneic bone marrow and T cells when treating mice with IFN- neutralizing antibodies. Likewise, ruxolitinib treatment protected ISCs from T cellmediated killing in vivo. Donor T cells, particularly T helper 1 cells, were activated and IFN-+. Transplanting IFN-depleted allogeneic T cells robustly reduced the ISC loss and allowed epithelial cell proliferation to increase.

Takashima and colleagues lastly investigated whether IFN- directly induces ISC apoptosis. Using tissue-specific depletion of IFN-R1, the authors found that epithelial loss of the receptor protects from the immune-mediated GVHD phenotype. IFN-R1 is expressed by both ISCs and Paneth cells, the epithelial component of the ISC niche (9). However, Paneth celldeficient organoids remained sensitive to both IFN- and allogeneic T cellmediated cytotoxicity. Likewise, T cells were able to reduce the number of organoids containing IFN-R1deficient Paneth cells, whereas organoids containing IFN-R1deficient ISC were protected from cytotoxicity. The authors demonstrated in further experiments that IFN- directly induces ISC apoptosis independent of Paneth cells (Fig. 1, B and C).

The study by Takashima et al. extends our knowledge on signaling between ISCs and immune cells, identifying ISCs as direct targets of IFN- secreted by T cells in immune-mediated intestinal damage (as caused by GVHD). In the 2015 study by Lindemans et al., this group already identified that interleukin-22 (IL-22) secreted by group 3 innate lymphoid cells (ILC3s) directly stimulates ISCs to proliferate and regenerate the intestinal epithelium upon inflammation-induced intestinal injury (4). Modulating the effects of T cellderived IFN- on ISC, for instance, by suppressing JAK/STAT signaling via ruxolitinib treatment, may provide a new therapeutic avenue to reducing GVHD-induced damage of the intestinal epithelium (10).

(A) ISCs maintain adult homeostasis of the intestinal epithelium. T lymphocytes patrol the intestine. (B) Takashima et al. show that in GVHD as modeled by BMT and aberrant activation of T lymphocytes, T cellderived IFN- directly acts on ISCs and induces apoptosis via JAK/STAT signaling. (C) Disease progression results in marked intestinal damage due to loss of ISCs and their niche.

Acknowledgments: Funding: K.K. is a long-term fellow of the Human Frontier Science Program Organization (LT771/2015). Competing interests: H.C. and K.K. are named inventors on patents or patents pending on Lgr5 stem cellbased organoid technology.

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IFN-: The T cell's license to kill stem cells in the inflamed intestine - Science

Pigs engineered to have a small amount of monkey cells have been brought to full term and were even born alive, surviving for a few days after birth. Although the piglets died, it is claimed the experiment - performed in China - marks a major milestone for the future of lab-grown organs.

"This is the first report of full-term pig-monkey chimeras," Tang Hai of the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing told New Scientist.

The research is part of an ongoing effort to develop animals - whether they are sheep or pigs - that can grow human organs we could then harvest for transplants, a process called xenogeneic organogenesis.

Research has been done on both pig and sheep embryos with transplanted human stem cells; in both cases, the embryos continued to develop until the experiment was deliberately terminated.

That's because, due to ethical concerns, these chimeras - organisms that incorporate the genetic material of another species - cannot be cultivated or studied in the later stages of embryonic development. Some scientists worry that some of the human stem cellscould end upin other parts of the animal or even in its brain, with unintended consequences.

For that reason, in this experiment the team used stem cells from crab-eating macaques (Macaca fascicularis). These were imbued with fluorescent proteins so that they would glow under fluorescent light, and derived to produce fluorescing embryonic cells.

These cells were then injected into over 4,000 five-day-old pig embryos fertilised using IVF; the modified pig embryos were subsequently implanted into sows.

This fiddly and painstaking work produced just 10 piglets that made it to full term and were born alive. And only two of these were chimeric, with between one in 1,000 and one in 10,000 functional monkey cells to pig cells.

The monkey cells had migrated to the heart, liver, lungs, spleen and skin of the piglet hosts, but were not found in other organs, such as testes and ovaries, due to the low rate of chimerism, the researchers said.

Sadly, before a week was out, the piglets died - not just the two chimeras, but the other eight normal piglets, too. Because all the pigs died, Hai told New Scientist, the cause of death likely had less to do with chimerism, and more to do with IVF - a procedure that is notoriously tricky in pigs.

The low chimerism rate is also somewhat discouraging. However, the researchers remain optimistic. Although the birth rate was low, and the pigs didn't survive, the team now has a wealth of data they can apply to future experiments.

The scientists are planning to try again, increasing the chimeric cell ratio. And they believe their data may help other scientists working in the field.

"Here, we have used monkey cells to explore the potential of reconstructing chimeric human organs in a large animal model," they wrote in their paper.

"We believe this work will facilitate the development of xenogeneic organogenesis by providing a better understanding of the processes of xenogeneic recognition, fate determination, and the proliferation and differentiation of primate stem cells during porcine development.

"The findings could pave the way toward overcoming the obstacles in the re-engineering of heterogeneous organs and achieve the ultimate goal of human organ reconstruction in a large animal."

The research has been published in Protein & Cell.

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Pig-Monkey Chimeras Have Been Brought to Term For The First Time - ScienceAlert

Organ donation involves removing a healthy organ from a donor and transplanting it into the body of a recipient who has a diseased organ that has failed irreversibly. The recipients survival often depends on getting an organ transplant.

There is a large need for organs by people affected with end-stage ailments, like diseases of the liver, lung, heart and kidney. A major obstacle to treating such people is that there arent enough donated organs around the world. In many countries, including in the West, the number of patients in the waiting list for organ transplants has progressively increased compared to the number of donor organs available.

And while the number of donors per million people is very low in many parts of the world, about 20-30 per million, its many times lower than this in India: less than 0.5 donor per million. Experts have estimated that a few lakh organs are required per year in India, although no more than 2-3% of this requirement is really met. The severe shortfall may need more effective propaganda, retrieval and use of donated organs.

There are also personal, religious and cultural barriers that make it hard for people to accept the idea of organ donation. Most religions dont appear to oppose organ donation, but people are often uncertain about these recommendations and so they are reluctant to donate. Judaism and Islam prohibit the desecration of corpses and stress on a complete body, timely rituals and burial within 24 hours after death. People may not prefer to donate organs of their near and dear after death, due to the mutilating effect of dissecting the body and removing its parts.

There are often logistical issues as well. Due to a lack of awareness of the donation procedure and its consequences, most people prefer receiving organs from live, instead of recently deceased, donors.

* * *

Organ donation came to be thanks to advances in surgical procedures that allowed doctors to replace a diseased or dying organ with a healthy foreign organ. These advances reflected the rise of the exchangeability of body parts. That is, clinicians began to view the body as a collection of organs and independent entities, such that they could be removed from one body and placed in another. By contrast, the older and more traditional view of the body regarded it as a complex, indivisible whole interacting with its environment. As the idea of exchangeability gained traction, organs became commodities with market value.

Also read:The Seamy Underbelly of Organ Transplantation in India

The advent of organ transplantation was a landmark in the history of medicine. Researchers had developed transplantation surgeries for small animals such as dogs, pigs and goats well before the 20th century. The organs in the human body that doctors most transplant are the kidney, heart and liver.

Murray and Merrill performed the first kidney transplant in the 1950s, from one monozygotic twin to another. Since the twins were genetically identical, they survived and lived for eight years after the procedure.

The first heart and liver transplants were undertaken in the mid-1960s. Christian Bernard, the famous South African surgeon, performed the first heart transplant in 1967, from a 25-year-old who was brain dead after an accident and to a 50-year-old man suffering from heart failure. In the same year, other doctors performed more than 100 heart transplants around the world, but the recipients in these transplants didnt live for more than a few days after. There were problems related to the health of the transplanted organs and the aftereffects of surgery.

An American surgeon named Thomas Starzl performed the first liver transplant in the mid-1960s. The first patient died immediately and after the surgery; a few more patients who received transplanted organs also died from infections and other illnesses within a few weeks.

Corneal grafts are a very well-known and effective form of organ or tissue donation. The cornea, which is the transparent structure on the front of the eye, consists of multiple layers of cells designed to be transparent. The cornea refracts light towards the eyes lens, located just behind it. Its relatively simpler to transplant cornea because it lacks blood vessels (i.e. since one doesnt need to restore blood vessels in the grafted tissue).

Another advantage is that the cornea is in a state of immune privilege: it is relatively protected from immune responses. So persons who undergo a corneal transplant dont need lifelong treatment with systemic drugs to suppress the immune system.

Corneal donation and transplantation have continuously evolved in theory and practice, and have a high rate of success. Franz Reisinger first attempted corneal grafts in the early 19th century, trying to transplant animal corneas into humans. He failed in repeated attempts. Reisinger also coined the term keratoplasty, which means surgery to the cornea.

Also read:Why Moral Exhortations Alone Will Not Boost Organ Donation in India

Only a few years later, Samuel Bigger, an Irish surgeon, treated a gazelle that had been blinded by a corneal scar by transplanting cornea from another gazelle.

A Viennese ophthalmologist named Edward Zirm performed the first successful corneal graft between two humans in the early 20th century.

* * *

One possible reason why organ transplants often dont have long-term success is the recipient. A person who is already sick due to a failed heart or liver is not likely to respond well to major surgery, and may have difficulty recovering from it. Similarly, an older patient may not be able to withstand the effects of surgery.

Another important factor is the recipients immune system, which could reject the donated organ. In 1979, doctors who just performed a liver transplant used a drug called cyclosporine to dampen the bodys immune response and thus spare the transplanted organ from attack. This occasion was a new step in the history of liver transplants. Cyclosporine improved the survival of over 70% of patients up to at least one year after surgery, and many patients survived for up to five yrs. Doctors have followed up with newer, better drugs to improve patients health outcomes since.

A third issue relates to an ethical question that researchers have flagged: a living donor has to undergo a major surgical procedure to donate an organ, and such procedures carry their own risks. Moreover, close relatives of a patient may be under pressure to agree to donate their organs, so they may not be necessarily free to decide for themselves. Another issue regards commercialisation: its very easy to provide monetary incentives to the poor and convince them to donate an organ in return. In such circumstances, the decision to donate an organ will not have been the result of free choice where it should be.

Such a market for kidneys is all too visible in India, where one finds advertisements for the sale of kidneys with hospitals involved in the business. Often, poor people are ready to donate their organs to make a lakh or two. Apart from theft and the black market for organs, monetary compensation for organs is legal in some parts of the world.

* * *

An alternative to overcome the shortage of organs for transplants is a xenotransplant: transplanting animal organs into humans. The principal animals that can potentially donate to humans are monkeys, since theyre most closely related to humans.

However, due to differences between the sizes of monkey and human organs, researchers have also considered pigs, whose organs are closer in dimensions as well as because pigs are easy to breed. Researchers are currently exploring these procedures in experiments.

Also read:Why Does Spain Lead the World in Organ Donation?

Another alternative for intact organs is stem cells, which scientists can grow in controlled environments, such as in a laboratory, and develop into miniature organs, or organoids. Using bioengineering techniques, they removed cells from an intact organ, such as a lung or trachea, such that the cells retain a skeleton of proteins and carbohydrates. Next, they populate these cells with stem cells and maintained them in a laboratory so that different types of cells grow inside the container. For example, scientists have grown multilayered corneas in a dish using a culture of stem cells and certain biomolecules.

Such advances in preserving and engineering tissues are help plug the gap between the demand for and supply of organs.

* * *

Its very important to preserve and properly store organs to ensure theyre in the best possible condition and retain their nature following transplantation. One particular concern here stems from the time and temperature of storage, which need to be carefully controlled to remain within specific limits depending on the organ and the type of death. Maintaining the right conditions ensures the organ remains viable after the recipient has received it. A heart may be stored for up to four hours, the lungs for up to six hours and the kidneys for longer periods, up to 18 hours.

A critical question to be addressed with regard to organ donation is the distinction between brain death and cardiac, or circulatory, death. A brain-dead patient will still have a functioning heart and may be on life support. However, brain-death means brain function has been completely and irreversibly lost.

For an organ donor, a criterion of either brain death or cardiac death may be taken under the definition of death. Indian law mentions two possibilities. One is in the Registration of Births and Deaths Act and the other, in the Transplantation of Human Organs and Tissues (THOT) Act. The former defines death as the permanent disappearance of all evidence of life at any time after live-birth has taken place. The THOT Act, on the other hand, defines a deceased person as one in whom permanent disappearance of all evidence of life occurs, by reason of brain stem death or in a cardiopulmonary sense, at any time after live-birth has taken place.

In many countries, both forms of death are considered acceptable for organ donation.

Chitra Kannabiranleads research on molecular genetics at the L.V. Prasad Eye Institute, Hyderabad.

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The Ins and Outs of Organ Donation - The Wire

BOSTON and LONDON, Dec. 08, 2019 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a leading commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies, will be presenting new registrational data from multiple programs at the 61st American Society of Hematology (ASH) Annual Meeting being held December 7-10, 2019 in Orlando, FL.

On Sunday, December 8, 2019, investigators will describe ongoing clinical progress for two lead development programs in the companys primary immune deficiencies portfolio: OTL-103, an investigational gene therapy in development for the treatment of Wiskott-Aldrich syndrome (WAS) at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy; and OTL-101, an investigational gene therapy in development for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID).

In addition, on Monday, December 9, 2019, investigators will deliver an oral presentation featuring updated data from the ongoing clinical proof-of-concept study of OTL-203, an investigational gene therapy in development for the treatment of mucopolysaccharidosis type I (MPS-I) at SR-Tiget.

To learn more about Orchards approach to ex vivo, autologous, hematopoietic stem cell (HSC) based gene therapy, conference attendees can visit booth #2228 in the Exhibition Hall.

Full presentation details are below:

Poster Presentation Details

Lentiviral Hematopoietic Stem and Progenitor Cell Gene Therapy for Wiskott-Aldrich Syndrome (WAS): Up to 8 Years of Follow up in 17 Subjects Treated Since 2010Publication Number: 3346Session: 801. Gene Therapy and Transfer: Poster IIDate and time: Sunday, December 8, 6:00-8:00pm ET

Lentiviral Gene Therapy with Autologous Hematopoietic Stem and Progenitor Cells (HSPCs) for the Treatment of Severe Combined Immune Deficiency Due to Adenosine Deaminase Deficiency (ADA-SCID): Results in an Expanded CohortPublication Number: 3345Session: 801. Gene Therapy and Transfer: Poster IIDate and time: Sunday, December 8, 6:00-8:00pm ET

Oral Presentation Details

Extensive Metabolic Correction of Hurler Disease by Hematopoietic Stem Cell-Based Gene Therapy: Preliminary Results from a Phase I/II TrialPublication Number: 607Session: 801. Gene Therapy and Transfer: Gene Therapies for Non-Malignant DisordersDate and time: Monday, December 9, 7:00am ET

About ADA-SCID and OTL-101Severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID) is a rare, life-threatening, inherited disease of the immune system caused by mutations in the ADA gene resulting in a lack of, or minimal, immune system development.1-4 The first symptoms of ADA-SCID typically manifest during infancy with recurrent severe bacterial, viral and fungal infections and overall failure to thrive, and without treatment the condition can be fatal within the first two years of life. The incidence of ADA-SCID is currently estimated to be one in 500,000 live births in the United States and between one in 200,000 and one in 1 million in Europe.3 OTL-101 is an autologous, ex vivo, hematopoietic stem cell-based gene therapy for the treatment of patients diagnosed with ADA-SCID being investigated in multiple clinical trials in the United States and Europe, including a registrational trial at the University of California, Los Angeles (UCLA). OTL-101 has received orphan drug designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of ADA-SCID, and Breakthrough Therapy Designation from the FDA.

About WAS and OTL-103Wiskott-Aldrich Syndrome (WAS) is a life-threatening inherited immune disorder characterized by autoimmunity and abnormal platelet function and manifests with recurrent, severe infections and severe bleeding episodes, which are the leading causes of death in this disease. Without treatment, the median survival for WAS patients is 14 years of age. Treatment with stem cell transplant carries significant risk of mortality and morbidities. OTL-103 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy developed for the treatment of WAS that Orchard acquired from GSK in April 2018 and has been developed at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. The global incidence of WAS is estimated to be about 100-260 births per year, with a global prevalence of 2,900-4,700 patients.

About MPS-I and OTL-203Mucopolysaccharidosis type I (MPS-I) is a rare inherited neurometabolic disease caused by a deficiency of the IDUA (alpha-L-iduronidase) lysosomal enzyme required to break down glycosaminoglycans (also known as GAGs or mucopolysaccharides). The accumulation of GAGs across multiple organ systems results in the symptoms of MPS-I including neurocognitive impairment, skeletal deformity, loss of vision and hearing, hydrocephalus, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births.5 There are three subtypes of MPS-I; approximately 60 percent of MPS-I patients have the severe Hurler subtype and, when untreated, these patients rarely live past the age of 10.Id Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms. OTL-203 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by the San Raffaele-Telethon Institute for Gene Therapy in Milan, Italy.

About Orchard Orchard Therapeutics is a fully integrated commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies.

Orchards portfolio of ex vivo, autologous, hematopoietic stem cell (HSC) based gene therapies includes Strimvelis, a gammaretroviral vector-based gene therapy and the first such treatment approved by the European Medicines Agency for severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID). Additional programs for neurometabolic disorders, primary immune deficiencies and hemoglobinopathies are all based on lentiviral vector-based gene modification of autologous HSCs and include three advanced registrational studies for metachromatic leukodystrophy (MLD), ADA-SCID and Wiskott-Aldrich syndrome (WAS), clinical programs for X-linked chronic granulomatous disease (X-CGD), transfusion-dependent beta-thalassemia (TDT) and mucopolysaccharidosis type I (MPS-I), as well as an extensive preclinical pipeline. Strimvelis, as well as the programs in MLD, WAS and TDT were acquired by Orchard from GSK in April 2018 and originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy initiated in 2010.

Orchard currently has offices in the UK and the U.S., including London, San Francisco and Boston.

Forward-Looking StatementsThis press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, intends, projects, and future or similar expressions that are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, Orchards expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product candidate or candidates referred to in this release, the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates, including any cryopreserved formulations of such product candidates, and the likelihood of approval of such product candidates by the applicable regulatory authorities. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be successfully developed or commercialized, the risk of cessation or delay of any of Orchards ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates, the delay of any of Orchards regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchards ability to commercialize its product candidates, if approved. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards annual report on Form 20-F for the year ended December 31, 2018 as filed with the U.S. Securities and Exchange Commission (SEC) on March 22, 2019, as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

1Orphanet. SCID due to ADA deficiency. 2Whitmore KV, Gaspar HB. Front Immunol. 2016;7:314. 3Kwan A, et al. JAMA. 2014;312:729-738. 4Sauer AV, et al. Front Immunol. 2012;3:265. 5Beck et al. The Natural History of MPS I: Global Perspectives from the MPS I Registry. Genetics in Medicine 2014, 16(10), 759.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaMolly CameronManager, Corporate Communications+1 978-339-3378media@orchard-tx.com

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Orchard Therapeutics Showcases Clinical Data at the 61st American Society of Hematology Annual Meeting - BioSpace

Black ChristmasUpdate of the 1974 holiday horror classic about sorority sisters stalked by a masked killer. With Imogen Poots, Aleyse Shannon, Lily Donoghue, Cary Elwes. Written by Sophia Takal, April Wolfe. Directed by Takal. (1:38) PG-13.

BombshellCharlize Theron, Nicole Kidman and Margot Robbie play Fox News employees whose allegations of sexual harassment help topple network founder Roger Ailes. With John Lithgow, Allison Janney, Connie Britton, Kate McKinnon. Written by Charles Randolph. Directed by Jay Roach. (1:48) R.

CunninghamDocumentary profile of influential dancer-choreographer Merce Cunningham includes archival footage plus re-creations of his works. Directed by Alla Kovgan. (1:33) PG.

The Death & Life of John F. DonovanAn actor recalls the letters he exchanged with a long-dead American television star. With Kit Harington, Natalie Portman, Jacob Tremblay, Susan Sarandon, Kathy Bates, Thandie Newton, Sarah Gadon. Written by Xavier Dolan, Jacob Tierney. Directed by Dolan. (2:03) R.

The Disappearance of My MotherWriter-director Beniamino Barrese profiles his reclusive mother, 1960s-era supermodel turned feminist activist Benedetta Barzini. In English and Italian with English subtitles. (1:34) NR.

First LoveThe brother of a famous but troubled actress is torn between selling his explosive tell-all book about their childhood or helping her after she suffers a nervous breakdown. With Annie Heise, Aaron Costa Ganis, Arye Gross, Mia Barron. Written and directed by Michael Masarof. (1:20) NR.

The Great WarAmerican soldiers during WWI go behind enemy lines to try to rescue a lost platoon. With Ron Perlman, Billy Zane, Bates Wilder. Written and directed by Steven Luke. (1:48) R.

Hell on the BorderA former slave gets a job as a lawman and goes on a manhunt in his fact-based western about the first black marshal in the Wild West. With David Gyashi, Frank Grillo, Ron Perlman. Written and directed by Wes Miller. (1:50) R.

A Hidden LifeWriter-director Terrence Malicks fact-based drama about an Austrian farmer who refused to fight for Nazis during WWII. With August Diehl, Valerie Pachner, Bruno Ganz, Matthias Schoenaerts. In English, German, Italian with English subtitles. (2:53) R.

Jumanji: The Next LevelDanny Glover and Danny DeVito join Dwayne Johnson, Jack Black, Kevin Hart and Karen Gillan in this sequel to the 2017 action adventure hit about young people trapped in a videogame. With Nick Jonas, Awkwafina. Written by Jake Kasdan, Jeff Pinkner, Scott Rosenberg; based on the book by Chris Van Allsburg. Directed by Kasdan. (1:54) PG-13.

Line of DescentAn organized-crime family in Delhi deals with threats from without and within. With Brendan Fraser, Max Beesley, Abhay Deol. In Hindi and English with English subtitles. (1:48) NR.

Midnight FamilyDocumentary about a family-run private ambulance service in Mexico City. Directed by Luke Lorentzen. In Spanish with English subtitles. (1:30) NR.

Mob TownMafia figures assemble for a summit in upstate New York in 1957 in this fact-based crime drama. With David Arquette, Jennifer Esposito, Jamie-Lynn Sigler, Robert Davi, Nick Cordero. Written by Jon Carlo and Joe Gilford. Directed by Danny A. Abeckaser. (1:30) R.

RabidA fashion designer experiences a horrifying transformation after undergoing an experimental stem-cell treatment following a car accident. With Laura Vandervoort, Benjamin Hollingsworth, Phil Brooks. Written by the Soska Sisters, John Serge; story by Serge. Directed by the Soska Sisters. (1:47) NR.

Richard JewellClint Eastwood directs this fact-based drama about the security guard falsely accused in the Centennial Park bombing during the 1996 Olympics in Atlanta. With Paul Walter Hauser, Sam Rockwell, Kathy Bates, Jon Hamm, Olivia Wilde, Ian Gomez. Written by Billy Ray; based on an article by Marie Brenner. (2:09) R.

SebergFrench New Wave actress Jean Seberg is targeted by the FBI for her political and romantic involvement with civil-rights activist Hakim Jamal during the 1960s in this fact-based drama. With Kristen Stewart, Anthony Mackie, Jack OConnell, Margaret Qualley, Zazie Beetz, Vince Vaughn. Written by Joe Shrapnel, Anna Waterhouse. Directed by Benedict Andrews. (1:36) R.

6 UndergroundRyan Reynolds stars in this Michael Bay action flick about a globe-trotting team of untraceable operatives dedicated to saving the world. With Mlanie Laurent, Corey Hawkins, Adria Arjona, Dave Franco. Written by Paul Wernick, Rhett Reese. (2:05) R.

Uncut GemsAdam Sandler stars as a desperate New York City jeweler juggling numerous deals in this crime thriller. With Lakeith Stanfield, Julia Fox, Kevin Garnett, Idina Menzel, Eric Bogosian, Judd Hirsch. Written by Josh Safdie, Benny Safdie, Ronald Bronstein. Directed by the Safdies. (2:15) R.

What She Said: The Art of Pauline KaelDocumentary on the longtime firebrand film critic of the New Yorker. With Alec Baldwin, Quentin Tarantino, David O. Russell, Francis Ford Coppola and Sarah Jessica Parker as the voice of Kael. Directed by Rob Garver. (1:38) NR.

Original post:
Movies opening in L.A. this week: 'Bombshell,' 'Jumanji: The Next Level' and more - Los Angeles Times

Data: ProQuest; Chart: Axios Visuals

Senate Intelligence Committee Chairman Richard Burr (R-N.C.) said this week that Ukraine meets the standard for election meddling that people first held Russia to. But that's not what the numbers show.

Why it matters: While Burr didn't draw a moral equivalence between Russia which committed several crimes on U.S. soil during the 2016 election and what we know about Ukraine, he muddled the debate in that direction.

What they're saying: "You considered Russia meddling with just the preference they had before you knew the rest of it," said Burr. "Apply the same standard to Ukraine."

But, but, but: Axios analyzed 1,847 news stories from 179 news sources that used the words "Russia," "election," "meddling" and their derivatives between Jan. 1, 2014, and Jan. 1, 2017. And it's pretty clear the concept of Russian election meddling didn't enter the American zeitgeist until the WikiLeaks email leaks on July 25.

Burr did not respond to a request for comment.

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The difference between Russia and Ukraine on election meddling - Axios

Vladimir Putin has contended with a nod to the chaos swirling in the West and to Russia's tumultuous history that the most precious thing a leader can offer his country is stability.

Why it matters: Putin has not made Russia rich, free or particularly happy. But he imposed stability and has maintained it for two decades through his own blend of force and skill. Putin's current term expires in 2024, and the constitution bars him from seeking another.

Zoom in: Dmitri Trenin, director of Carnegie Moscow and a former Russian military officer, does not believe Putin will change the constitution to become "president for life." Thus, he says, 2024 will be the last year that Vladimir Putin will be president of Russia."

Two specific methods have been floated, beyond a constitutional change:

1. Putin forms a commonwealth with Belarus, maintaining presidencies in both countries but placing himself above them.

2. Putin builds himself another powerful role like chair of the National Security Council and oversees a staged transition from that perch.

Where things stand: Putin will be 71 when his term expires. He told the FT in June that he had been thinking about succession "since 2000."

The big picture: The "mafia-esque structure" Putin has built requires loyalty within elite circles and support from the public, says Alina Polyakova of Brookings.

Zoom out: The Russian system collapsed twice in the 20th century, in 1917 and 19891991.

The bottom line: "This transition will never be very smooth and will never be very happy even," says Trenin. But history will judge Putin on its outcome.

Putin has left the Kremlin once before, when he first ran up against term limits in 2008 and became prime minister.

Behind the scenes: "We always had an assessment, perhaps exaggerated, that Putin was the main decision-maker and [Dmitry] Medvedev was just a figurehead," says Michael McFaul, who was Barack Obama's Russia adviser and later ambassador to Moscow.

Flash forward: We always thought Putin was coming back," McFaul continues, "but there was enough ambiguity that you could hold open the possibility that maybe Medvedev would stay.

The bottom line: [Putin], like a lot of autocrats, convinced himself that he was the indispensable player and that Russia needed his strong hand in the Kremlin," says William Burns, who was then deputy secretary of state.

McFaul originally thought Putin was exaggerating both the threat to his regime during the 2012 protests and the role he attributed to the U.S.

Behind the scenes: He had no incentive to tell [national security adviser] Tom Donilon or [Secretary of State] John Kerry that were trying to overthrow the regime. Thats supposed to be for the workers and the peasants. But in those conversations, I heard a level of suspicion he just assigned all kinds of power to the United States and especially the CIA that they dont have."

"I think psychologists would call it projection," Burns says, noting that Putin had suspicion drilled into him as a KGB officer.

Former Secretary of Defense Ash Carter is more blunt. "One of his objectives is to screw us. That, unlike Syria or nuclear proliferation, is not an area where I am willing to reach common ground."

The bottom line: "Declining powers in a lot of ways as Putin reminded us can be at least as disruptive as rising powers," says Burns.

Putin issued that reminder in 2014 when he annexed Crimea and launched the war in eastern Ukraine.

The big picture: Putin views Ukraine as firmly within Russia's sphere of influence, and he saw Kiev's sudden shift toward the West as an existential threat.

Behind the scenes: We didnt have the resources devoted to Russia that we needed to understand what Russia was doing under Putin," says Michael Morell, a former CIA deputy director, noting that the invasions of Ukraine and of Georgia in 2008 took Washington utterly by surprise.

The bottom line: Just a few years after being dismissed by Obama as a "regional power," Russia was being discussed in Washington as one of three key players in an era of "great power competition."

Two of those three powers inaugurated a 1,800-mile-long symbol of their burgeoning partnership yesterday.

Driving the news: The Power of Siberia pipeline will deliver Russian gas to China and is expected to generate $400 billion for Russian state coffers, per Reuters.

The big picture: Asked about the relationship with his giant neighbor, Putin told the FT, "We have sufficient eggs, but there are not too many baskets to put those eggs in."

Between the lines: He's squeezing everything he can out of a relationship that currently provides massive economic and strategic benefits, but is also increasingly imbalanced.

The bottom line: Right now its a pretty strong marriage of convenience," says Burns, "born of a shared interest in chipping away at an American-led order."

Putin looks at China's rise, Trump's election and Europe's identity crisis and reaches a provocative conclusion: "the liberal idea has become obsolete."

Why it matters: Putin's alternative path has been embraced by high-profile politicians and a widening slice of the European electorate:

Zoom out: Putinism is a new set of ideas that is exportable," McFaul says, noting the rise of Europe's far right. Hes not alone in this fight.

The little-known KGB veteran who thrived in the shadows, underestimated and overlooked, has grown into a giant.

He's not only one of the world's most powerful men, he may be one of the richest. Anders slund of the Atlantic Council pegs his net worth at $100 billion to $160 billion, including a $1 billion palace on the Black Sea.

After 20 years at the top of that pyramid, with all the wealth and all the enemies he's accumulated along the way, leaving power would be perilous.

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20 Years of Putin: The pinnacle of power and the fear of losing it - Axios

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

- Cures -

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

- Bioterrorism -

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

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2019: the year gene therapy came of age - RTL Today