The mystery of PD-1 immunotherapy resistance was first unveiled
Recently, researchers at the University of California, Los Angeles, first discovered how advanced melanoma is resistant to immunotherapy. The study, funded primarily by the National Cancer Institute, was published in the latest issue of the New England Journal of Medicine.
We are no stranger to the research leader, Dr. Antoni Ribas, the prestigious director of the Cancer Immunology Program at UCLA, who was a principal investigator of the large phase 1 clinical trial of the anti-PD-1 drug Keytruda (pembrolizumab). . As an immunological checkpoint inhibitor, Keytruda binds to PD-1 molecules on T cells, activates the suppressed immune response, and enhances the body's own immune function to protect against tumor cells. He commented on the study entitled "Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma": "This will help us better design the next generation of cancer immunotherapy."
It is estimated that about 40% of patients with advanced melanoma (the most deadly form of skin cancer) will initially respond to immunotherapy, but a quarter of patients will relapse within three years of treatment.
Researchers at the University of California, Los Angeles, collected melanoma biopsies from relapsed patients and analyzed the genome-wide sequence of tumor cells before and after Keytruda treatment. Among them, one patient's tumor cells have lost a gene called B2M, which encodes "antigen-presenting protein beta-2-microglobulin", thus changing the immune system to recognize cancer cells. the way. In the other two patients, tumors have functional defects in the JAK1 and JAK2 genes, limiting the ability of the immune system to kill cancer cells.
Although these patients were treated with Keytruda, Dr. Antoni Ribas believes the results can be extended to all PD-1 related therapies. He also said that identifying resistance mechanisms may help explain why some patients do not respond to immunotherapy.
“If we delve into the mechanisms of resistance, we may be able to design better treatments. There is still a lot of work to be done to develop drugs that target these mutations.â€
Indeed, the essence of precision medicine lies in understanding the specific genetic background of each patient and designing the most individualized medical plan to prevent, cure, and cure the fastest, most accurate, safest and most effective. We are very happy to see the ever-changing technological developments and promote a better quality of life for people all over the world.
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