Alan N. Houghton, MD
Vice Chairman for Academic Affairs
Department of Medicine
Ludwig Clinical Chair
Memorial Sloan-Kettering Cancer Center
New York, New York
2013-2014 BCRF Project:
(The Peter Jay Sharp Foundation Award
Co-Investigators: Larry Norton, MD, Memorial Sloan-Kettering Cancer Center, New York, NY; Jedd Wolchok, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York, NY
Effective vaccination against breast cancer is difficult because breast cancer arises from cells that were once normal and our bodies have elaborate controls to stop the immune system from attacking our own tissues. However, research supported by the Peter Jay Sharp Foundation/BCRF has discovered a way to trick the immune system by vaccinating against cancer using a vaccine from a different species. The immune system recognizes the vaccine as “foreign” and generates an immune response to destroy breast cancer cells as if they were foreign invaders. This research has moved from the laboratory to patients— the Investigational New Drug (IND) application for a vaccine created under this support was approved by the Food and Drug Administration (FDA) and the clinical trial to test the first-generation vaccine against breast cancer is accruing patients. Specifically, with support from Peter Jay Sharp Foundation/BCRF, during this past year this team has been able to: (1) continue to accrue patients to the last cohort of a clinical study evaluating the HER2/neu DNA vaccine in patients with breast cancer and all patients in these cohorts have completed all vaccinations with no significant toxicity, (2) evaluate the efficacy of HER2/neu antibody (Equivalent to Herceptin) in combination with anti-CTLA-4 (equivalent of Ipilimumab), (3) Evaluate the combination of gemcitabine in combination with anti-CTLA-4, and (4) continue to accrue women with early-stage breast cancer to a clinical trial of ipilimumab and/or cryoablation. In the future, this group will continue their investigation of the optimal means to use the immune system to treat breast cancer. In addition to completing accrual to the HER2/new DNA vaccine study, in the coming year the researchers plan to further evaluate the efficacy of the combination therapy of the monoclonal antibody to HER2/neu (the equivalent of Herceptin in clinic) in combination with immunomodulatory antibodies (CTLA-4, CD137, PD-1, OX40, GITR) and determine the mechanism of action for the optimal combination; investigate radiation in combination with immune modulation in a laboratory model of breast cancer; and evaluate the effects of immunomodulatory antibodies in combination with chemotherapy. Further, they will continue accrual to the ipilimumab trial. Assuming that the primary end-point of safety and tolerability is met, which seems reasonable a larger randomized phase 2 study will be undertaken.
During this past six months this research team has been able to: (1) Finish accrual to the last cohort of a clinical study evaluating the HER2/neu DNA vaccine in patients with breast cancer, (2) optimize a schedule for combining anti-Her2/neu (equivalent to Herceptin) with anti-CTLA-4 (equivalent of ipilimumab) and gemcitabine that will result in the greatest tumor protection (3) Evaluate the combination of gemcitabine with other immunomodulatory antibodies (4) continue to collect safety data from patients enrolled on the clinical trial of ipilimumab and/or cryoablation, (5) conduct the immune monitoring of these patients. It is anticipated that a related abstract will be submitted for presentation at ASCO in June 2014.
The researchers will continue their investigation of the optimal means to use the immune system to treat breast cancer.
Alan Houghton is Chairman of the Immunology Program and Chief of the Clinical Immunology Service at Memorial Sloan-Kettering Cancer Center, and Head of the Melanoma Disease Management Team and the Laboratory of Tumor Immunology. He holds the Virginia and Daniel K. Ludwig chair in Clinical Investigation and is Professor of Medicine and Immunology at Cornell University where he also Chairs the Graduate Program in Immunology (Sloan-Kettering Division).
He is an internationally known expert in cancer immunology, studying how the immune system recognizes and rejects cancer. He is also recognized for his expertise in the treatment of melanoma and for the creation of novel treatments for this deadly form of skin cancer. Dr. Houghton conducted a landmark trial that produced the first significant regression of a solid tumor with a monoclonal antibody. He and his colleagues are presently leading clinical trials in cancer vaccines developed in their laboratories that are currently undergoing clinical trials to prevent cancer recurrence in several solid tumors including breast, prostate, melanoma and small cell lung cancer.
Dr. Houghton was most recently the recipient of the Award for Excellence in Medicine from the Society of Memorial Sloan-Kettering Cancer Center and the Distinguished Achievement and Leadership Award from the American Skin Association, and is a past recipient of the C. Chester Stock Award for Cancer Research and the Boyer Award for Clinical Research. He is an Editor of the Journal of Experimental Medicine and other journals, and is a member of numerous scientific organizations including honorary elections to The American Society of Clinical Investigation and the Association of American Physicians. He has published more than 200 papers and books and served on numerous study sections at the National Institutes of Health, American Cancer Society and the Department of Defense.