Drug helps defense system fight cancer

June 3, 2012 | Source: New York Times

An experimental drug is showing promise in disabling a molecular shield that repels attacks from the immune system, causing shrinkage of some lung, skin and kidney cancers that had defied treatment with existing drugs.

“We are seeing responses in heavily treated patients — three different cancers, one drug,” Dr. Suzanne L. Topalian, a melanoma specialist at Johns Hopkins University and lead investigator in the study, said in an interview. “This is a group of patients whose life expectancy was measured in a few months.”

The results are from an early clinical trial, and it is not clear whether the drug, developed by Bristol-Myers Squibb, will actually help people live longer. But Dr. Topalian said she was optimistic because when tumors did shrink, they often did not grow back again for more than a year.

The drug, BMS-936558, blocks a protein called PD-1 (programmed death 1). 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. This is apparently a way that the body regulates the immune system, to avoid an overreaction.

But many cancer cells make PD-L1, which allows them to disarm the T cells just as they are coming to attack the tumor. The Bristol drug is a monoclonal antibody that blocks PD-1 from binding to PD-L1. PD-1 blockers appear to free up the immune system only around the tumor, rather than more generally.

That could mean that PD-1 will have “fewer side effects and greater anti-tumor activity,” than drugs like Yervoy, Dr. Antoni Ribas, a melanoma specialist at the University of California, Los Angeles, said in an editorial being published in the New England Journal of Medicine.

Bristol-Myers plans to begin more clinical trials aimed at winning approval of the drug to treat non-small-cell lung cancer, kidney cancer and melanoma, a deadly skin cancer.

Others pursuing drugs that block the action of PD-1 include Merck; the Genentech unit of Roche; GlaxoSmithKline, working with a small Maryland company called Amplimmune; and Teva working with an Israeli biotech company, CureTech.