StemCell Therapy

Todays cancer therapies are often hailed for their ability to deliver a more personalized approach one that considers the mutations lurking in a patients tumor or proteins expressed on the surface of a patients T cells and while current therapies are largely considered improvements from some past therapies, they still stand to benefit from even more personalization.

In particular, therapies can become more personalized if they address how a persons own genomics influence response to treatment, also known as pharmacogenomics, and this type of evidence is emerging for immune checkpoint inhibitors.

Specifically, a better understanding of T-cell behavior during immune checkpoint blockade is starting to form.

Its the T cells that actually do the work, Timothy Chan, MD, PhD, Memorial Sloan Kettering Cancer Center, New York City, told Cancer Therapy Advisor. He explained that because of this, its even more important that everybodys own individual genetic make-up is examined.

In a study recently published in Nature Medicine, Dr Chan and colleagues looked at the diversity of human leukocyte antigen class I (HLA-I) genes, which help the immune system fight off viruses, and juxtaposed it with the efficacy of antiCTLA-4 or antiPD-1/PD-L1 inhibitor therapy in patients with metastatic melanoma or non-small cell lung cancer. The study revealed that greater evolutionary HLA-1 diversity was linked to higher T-cell infiltration into the tumor and better response to immune checkpoint blockade.1

If youre very diverse, youre likely to benefit, Dr Chan explained. It is probably the most powerful pharmacogenomics signal that I have personally seen.

HLA diversity can vary depending on where a person lives in the world, with more isolated populations being more genetically homogenous and having lower HLA diversity, and the greater the diversity, the more efficient the immune system is at fighting off infections. However, while HLA diversity is a factor thats controlled for in vaccine clinical trials, it is not routinely examined or measured in cancer clinical trials.

I actually think that that is one of the missing pieces in understanding why some trials are positive [and] some trials are negative, Dr Chan said. Its because nobody is controlling for this one aspect that is critical for the success of immune checkpoint therapy.

In fact, the lack of consideration of HLA diversity in clinical trials may even explain the mixed success tumor mutation burden has seen as a biomarker for response to immune checkpoint inhibitors to date.2 According to Dr Chan, tumor mutation burden is only half the story and that trial investigators really need to look at the other half HLA diversity.

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Immune Checkpoint Inhibitors on Track for Better Personalization - Cancer Therapy Advisor

This entry was posted on December 17, 2019 at 8:41 am and is filed under Immune System. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |