Alan N. Houghton, MD

2009-2010 BCRF Project:
The Peter Jay Sharp Foundation Award
Co-Investigator: Larry Norton, MD, Memorial Sloan-Kettering Cancer Center, New York

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 has opened.

Specifically, with support from Peter Jay Sharp Foundation/BCRF, during this past year the researchers have been able to: (1) complete accrual of the first cohort to a clinical study evaluating the HER2/neu DNA vaccine in patients with breast cancer, (2) evaluate the efficacy of antibody plus DNA vaccine therapy in combination with anti-CTLA-4 in a melanoma model (this therapy will be tested in a breast cancer model within the next funding year), (3) test the combination therapy of an immunomodulatory molecule and a chemotherapeutic drug which promoted the regression of established tumors and/or significantly prolonged survival in a breast cancer model, (4) explore the mechanism by which the anthrax receptor functions in immune responses.

Although the process of creating a new experimental therapy, such as a vaccine, including the basic research, preclinical studies, protocol development, safety evaluation and manufacturing, normally takes many years, Peter Jay Sharp Foundation/BCRF support has allowed the researchers to move rapidly, shaving years off of this process. The future direction of their work will focus on completing accrual to the HER2 clinical trial. They will also further optimize an immunotherapeutic approach in the treatment of breast cancer by combining their DNA vaccines with immunomodulatory molecules.

Bio:
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.