Another breakthrough in immunotherapy

We are still not curing advanced cancers with immunologic therapy, but an important step forward was announced today at the annual meeting of the American Society of Clinical Oncology (ASCO). Both at ASCO and simultaneously published online in the New England Journal of Medicine were the results of several trials of an antibody to PL-1, a receptor on immune T cells that normally dampens the immune system. Our immune system deploys antibodies and cell-killing activity against foreign invaders, but has to rev back down after the infection and also has to develop a tolerance to "self" antigens on normal tissue. This dampening system is often hijacked by tumor cells to avoid immune destruction. There is already a drug approved that blocks the dampening effect and allows the immune system to better unleash its effects on tumor cells. Yervoy (ipilumumab) blocks an immune-dampening receptor call CTLA-4 and has been shown to improve survival in patients with melanoma. Another such receptor called PD-1 (for "programmed death"), can be targeted with an anti-PD1 antibody. Two large early phase trials with this drug (known as BMS-936558) presented today reported activity in patients, with about 18 percent of patients with lung cancer having a response in addition to 30 percent of patients with kidney cancer and melanoma--the two cancer types that can respond to immunotherapy even though only about 5 to 10 percent are long-term remissions with the non-specific immune stimulator, interleukin 2. The potential addition of lung cancer to immune-responsive cancer is clearly important--there is excitement already about vaccines that are in late-phase testing for lung cancer, as well. However, this new antibody, similar to Yervoy, appears to cause reciprocal immune injury to normal tissue, with these trials reporting inflammation of the colon, lung and endocrine glands. Unleashing the immune system in other cancers will require further study and more understanding about the immune regulatory controls. Extending this to other cancers, testing it earlier to prevent metastases in the first place, and refining the immune response to spare normal tissue will all be important priorities for the future.