The scientist whose discoveries led to the first drug approved for metastatic melanoma by “treating the immune system, not the cancer,” also is the first to receive the AACR-CRI Lloyd J. Old Award in Cancer Immunology.
James Allison, Ph.D., professor and chair of The University of Texas MD Anderson Cancer Center Department of Immunology, was honored today at the AACR Annual Meeting 2013 in Washington, D.C.
The American Association for Cancer Research and the Cancer Research Institute launched the award to recognize the increasing importance of immunology in cancer treatment and to honor Old, who died last year at 78 after a path-breaking career in immunology research and leadership.
“I'm delighted and honored to be given this award named for Lloyd Old, who is widely considered to be the father of cancer immunotherapy. I was fortunate in knowing Dr. Old as a mentor, but also as a close friend,” Allison said.
“This new award by AACR and CRI recognizes individuals, but it's also gratifying recognition of the growing prominence of immune therapy and of our progress towards fulfilling Dr. Old's goal of unleashing the immune system against cancer,” Allison said.
Antibody blocks inhibitor of T cell response
Allison's basic science discoveries about the immune system led to his identification and development of ipilimumab, known commercially as Yervoy, a monoclonal antibody that blocks a molecule on the surface of T cells that acts as a brake on the immune system.
About 23 percent of patients with late stage metastatic melanoma who took ipilimumab in clinical trials have lived for five years or longer, unheard of in stage 4 melanoma patients. The drug was approved by the U.S. Food and Drug Administration in May 2011.
“Our goal is to accelerate the transition of new drugs and rational combinations based on mechanistic insight into the clinic,” Allison said. “These approaches have proven effective in the treatment of melanoma and prostate cancer, and there is no reason that immunotherapy, since it targets the immune system and not the cancer cell, shouldn't be effective against a broad range of cancer types.”
The drug has been used in more than 4,000 patients with a variety of cancers, including clinical trials for prostate, renal, lung and ovarian cancers.
The immune system routinely recognizes and destroys abnormal cells, but cancer cells manage to evade detection and attack. Old and colleagues believed that the immune system is ideally suited to wipe out cancer if those problems can be overcome, an unpopular view for decades.
Allison's discoveries in T cell biology built the foundation for him to identify and advance ipilimumab. T cells are lymphocytes, a white blood cell with receptors to recognize and bind to antigens, allowing the T cells to launch a customized attack on viruses, bacteria, abnormal cells and proteins.
•The T cell antigen receptor used by T cells to bind to and recognize antigens.
•T cells require a second signal to launch an immune response after they've bound to an antigen. B7 molecules on presenting cells must engage a surface molecule called CD28 on the T cell.
•An immune-inhibiting molecule called CTLA-4 inhibits activated T cells to protect normal tissue from attack. CTLA-4 apparently also protects cancer cells from attack.
The University of Texas MD Anderson Cancer Center