From a seeking alpha story about BMY's approach:
"PD-1 is a protein on the surface of activated T cells, the warriors of the immune system. If another
molecule, called PD-L1, binds to PD-1, the T cell dies or becomes docile. In other words, when PD-1 and PD-L1 join together, they form a biochemical "shield" that makes tumor cells invisible in a sense to the immune system.
PD-1 may explain many past failures in cancer immunotherapy. Even though many experimental cancer vaccines managed to spur an immune response, PD-1 cancelled that response at the site of the tumor. Apparently PD-1 helps the body regulate the immune system, to avoid an overreaction. Many different types of cancer cells make PD-L1, which allows them to disarm the T cells just as they arrive to attack the tumor.
Bristol's drug is a monoclonal antibody that blocks PD-1 from binding to PD-L1. BMS-936558 blocks PD-1, and BMS-936559 blocks PD-L1. The drugs are given intravenously in an outpatient clinic every two weeks, and patients could remain in treatment for up to two years. These drugs could reduce tumor mass in different cancers. Tumors shrank significantly in 18% of lung cancer patients, 28% of melanoma patients and 27% of kidney cancer patients. These rates compare favorably with some existing drugs. But the drug did not appear to work for patients with prostate or colon cancer. About 14% of the patients experienced severe side effects and three patients died from inflammation of the lung that was apparently tied to the drug."
BMS is now testing BMS-936558 in combination with Yervoy in about 100 people with advanced melanoma.
Because CTLA-4 binding can happen between T cells and many cells in the body, while PD-1's binding partner, PD-L1, is found only on tumor cells, researchers are hoping that these new immunotherapy drugs will ultimately prove safer and more effective than Yervoy. Sensitizing the tumor to killing by the immune system could work better because it shouldn't cause the side effects seen when patients' immune systems are over-activated and start attacking other non-cancerous tissue.
Perhaps an anti-PD-L1 will be the next-next big thing in immunotherapy. It is estimated that realistically the earliest anti-PD-1 will appear on the market is 2016. Several other drugmakers are working on PD-1 targeting drugs, like Merck (MRK), Roche, a small Maryland company called Amplimmune, and the Israeli company CureTech.
The believers are the responders who received Allovectin-7.
We will soon see the durable overall response rate and the median overall survival data of these stage 3 and stage 4 metastatic melanoma patients to prove that A-7 in the special protocol application will get FDA approval as the safest and most effective cancer vaccine to come to market.