Welcome to the birthplace of immunotherapy. When the first drug for the rare skin cancer Merkel cell carcinoma won approval in March, it marked another milestone in a celebrated new treatment approach that traces its roots to research by scientists at Harvard Medical School and Dana-Farber Cancer Institute. The drug, Bavencio, developed by EMD Serono of Rockland, targets what’s called the PD-1 pathway, molecules that bind to a protein and act as a brake on the immune system’s ability to fend off tumors. By releasing the brake, Bavencio lets the immune system do its job: attack cancer cells.
Other high-profile immunotherapies, such as Opdivo and Keytruda, also work as PD-1 inhibitors. As regulators approve these types of immunotherapies for new uses, they are gaining traction for patients against deadly cancers, including metastatic melanoma, Hodgkin’s lymphoma, and head and neck malignancies. In addition to improving responses, the new therapies avoid the worst side effects of chemotherapy, such as hair loss and anemia.
“It’s like being there at the dawn of a revolution,” says immunologist Gordon Freeman, whose Dana-Farber lab pioneered the understanding of how to disable PD-1 and unleash the immune system. “This discovery has released a flood tide of energy in academic and pharma labs.”
Freeman, a pioneer of PD-1 research, had plenty of help over the past two decades from scientists around the world — and locally. His wife, Harvard microbiology professor Arlene Sharpe, engineered a mouse lacking a key immune-suppressing gene in the 1990s. Immunotherapy was experimental until recently, but it may soon supplant chemotherapy — which kills cancer cells with chemicals — as the dominant approach in treatment and research.
Much work remains, though. More than 50,000 patients have been treated with PD-1 inhibitors, and so far the only unqualified success has been for Hodgkin’s lymphoma, which has seen an 82 percent response rate. Response rates for others have ranged from 15 percent to 35 percent.