29th Annual Dolan Lecture

Thursday, October 27, 2016

5:30pm - 6:00pm Pre-reception
6:00pm - 7:30pm Lecture

Reception immediately following the program

The John T. Hazel, M.D. Conference Center
The Virginia Hospital Center, Arlington, VA

Cancer Immunotherapy: A Journey from the Wilderness to the Promised Land

On February 4, 2016, the American Society of Clinical Oncology released its annual report, "Clinical Cancer Advances 2016". The 2016 advance of the year is cancer immunotherapy. This is a cancer treatment designed to boot the body's natural defenses to fight cancer. These new therapies give hope to cancer patients, and at the same time, are opening new paths for future research.

Harnessing the body’s immune system to control cancer has long been a dream of the cancer community, but only recently has our understanding of tumor immunology advanced to the point where this is becoming a reality. Investigations in the 1980s established that activated T cells could produce durable clinical responses and cures in a subset of patients with metastatic melanoma or kidney cancer. Subsequent research, spearheaded by the Surgery Branch of the National Cancer Institute, determined that many tumors were infiltrated with tumor-infiltrating lymphocytes (TILs) that, when removed, reactivated and expanded outside the body and re-administered, could eradicate melanoma in 20% of patients not responsive to HD IL-2.

These seminal observations sustained interest in cancer immunotherapy and spawned efforts to reactivate TILs within the tumor itself. These efforts were rewarded by the discovery of immune checkpoints, such as programmed death 1 (PD1) and its ligand 1 (PD-L1), which function to dampen immune responses in the tumor microenvironment and the observation that blocking of these checkpoints could restore specific anti-tumor immunity.

Antibodies against PD-1/PD-L1 pathway have produced durable tumor responses, not only in patients with advanced melanoma and kidney cancer, but also in at least 18 other tumor types, revolutionizing both immunotherapy and the broader field of cancer therapy. The tolerability of PD-1 pathway blocking agents made combinations with various other forms of cancer therapy and other immunomodulatory agents possible. Initial combinations of anti-PD-1 antibodies with antibodies blocking cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), another immune checkpoint, produced antitumor activity superior to anti–PD-1 monotherapy in patients with melanoma, establishing proof of principle that these immunosuppressive mechanisms were not redundant. This observaton paved the way for the further exploration of this approach in other cancers and the study of other combination immunotherapy regimens.

Today the use of these immunotherapy agents alone and in combinations is revolutionizing the way we treat and even think about cancer and promises to become the dominant treatment strategy for many if not most cancers for the forseeable future.