In the June 2 New York Times, Memorial Sloan Kettering oncologist Jedd Wolchok discussed how new cancer immunotherapies are allowing patients to survive longer than ever before. The interview took place at the 2014 meeting of the American Society of Clinical Oncology in Chicago.
In May 2014, Dr. Wolchok also described the stunning success of cancer immunotherapy in detail in an article for Scientific American.
Memorial Sloan Kettering medical oncologist Jedd Wolchok is featured in the May issue of Scientific American and on its website describing the new generation of cancer therapies that unleash the immune system to attack tumors. This new approach, which Memorial Sloan Kettering physician-scientists played a major role in developing, is producing stunning results when combined with standard anticancer therapies.
“I believe it is finally time to start thinking realistically about long-term remissions, even cures, because we can now combine standard therapies that target the tumor with immunotherapies that boost a patient’s own defenses,” Dr. Wolchok writes in “New Drugs Free the Immune System to Fight Cancer.” (Subscription is required for access to the full article.)
On its website, Scientific American also has a brief commentary about the feature, along with a video of Dr. Wolchok presenting a comprehensive overview of the new approach. In his article, Dr. Wolchok recaps the history of attempts to harness host defenses against cancer, which dates back more than 100 years. In the 1890s, William Coley, a surgeon at New York Cancer Hospital (the predecessor to Memorial Sloan Kettering), discovered that cancer patients who suffered from infections after surgery often fared better than those who did not. Dr. Coley hypothesized that the body’s defense system, which had been mobilized against the pathogen, could also affect the tumor. In the ensuing decades, scientists learned a great deal about the immune system’s workings without much success in translating their findings into cancer therapies.
Taking off the Brakes
Then in the 1990s, researchers discovered the importance of CTLA-4, a protein receptor on the surface of immune cells called T cells that puts the brakes on these cells and prevents them from carrying out attacks. Immunologist James Allison identified an antibody that blocks CTLA-4 and showed that turning off those brakes allows T cells to destroy cancer in mice. (Dr. Allison, who spent nearly a decade of his career at Memorial Sloan Kettering before leaving in 2012, is now at MD Anderson Cancer Center in Houston.)
Striking Clinical Success
Anti-CTLA-4 eventually became ipilimumab (YervoyTM), a drug approved in 2011 for the treatment of metastatic melanoma, the most deadly form of skin cancer. Dr. Allison and Dr. Wolchok helped guide the development of ipilimumab from the first laboratory studies through the late-stage clinical trials that led to the drug’s approval. Results of the latest clinical studies show that just over 20 percent of patients with metastatic melanoma treated with ipilimumab show long-term control of their disease, remaining alive for more than three years after treatment. (Previously, median life expectancy was seven to eight months.)
Researchers have found a second immune-system-braking molecule, called PD-1, which can also be blocked with antibodies. Immunotherapies targeting PD-1 have proved successful in treating lung cancer. “No longer can skeptical clinicians dismiss the approach as likely to be viable for only a few specific kinds of tumors,” Dr. Wolchok writes. “Odds are this approach will soon join chemotherapy and radiation as a standard treatment for many kinds of tumors.”
Dr. Wolchok’s research on immune therapies for melanoma continues, including a study last year that found more than half of patients with advanced skin melanoma experienced tumor shrinkage of more than 80 percent when given the combination of ipilimumab and the antibody drug nivolumab, which blocks PD-1.
Dr. Wolchok describes the optimism that has grown throughout the medical community over the last few years about immunotherapy treatments in patients with advanced leukemia and kidney and lung cancers. “Although immunotherapy is by no means a panacea, the recent advances may allow us to make significantly more progress against the later stages of cancer than we have been able to achieve in recent decades,” he writes.