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A key factor in the development of melanoma is the ability of cancerous cells to evade the body’s natural defenses against foreign and diseased cells. Johns Hopkins scientists are studying how to educate the immune system to recognize and kill melanoma cells in a variety of ways, including arming immune T cells with specific capabilities in detecting melanoma.
Researchers at Johns Hopkins Kimmel Cancer Center are leading the way in developing novel immunotherapies called anti-PD-1 and anti-PD-L1 for people with advanced melanomas. The therapies aim not to kill cancer cells directly but to block a pathway that shields tumor cells from immune system components able and poised to fight cancer.
The pathway includes two proteins called programmed death-1 (PD-1), which is expressed on the surface of immune cells, and programmed death ligand-1 (PD-L1), which is expressed on cancer cells. When PD-1 and PD-L1 join together, they form a biochemical "shield" protecting tumor cells from being destroyed by the immune system. Another protein involved in the pathway and also expressed by cells in the immune system, programmed death ligand -2 (PD-L2), was originally discovered by Johns Hopkins investigators in 2001.
“Tumors can co-opt PD-1 to their own advantage to fly below the radar of the immune system,” explains Suzanne Topalian, M.D., director of the melanoma program at Johns Hopkins, and a professor of surgery and oncology. “By using a blocking agent against PD-1, we can interrupt that shield protecting the tumor from immune destruction.”
In collaboration with pharmaceutical companies and other medical centers, new drugs blocking these interactions are currently in clinical testing. Promising results from these clinical trials have shown activity not only against advanced melanoma but also against non-small cell lung cancers and kidney cancers. Thousands of patients worldwide have been treated with anti-PD-1 or anti-PD-L1 drugs produced by several pharmaceutical companies, and early encouraging results have supported ongoing wider testing in larger groups of patients for potential approval by the U.S. Food and Drug Administration.
In addition, Johns Hopkins investigators devised laboratory studies yielding preliminary evidence for tumor biopsy markers associated with a greater likelihood of tumor response to anti-PD-1 therapy. These studies have led to a greater understanding of how these promising new drugs work. A new pipeline of immune-modulating drugs that work by similar but distinct mechanisms is now entering testing in our clinics.
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