WASHINGTON, D.C. - 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.Allison discovered:
- 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.
Ipilimumab is an antibody that blocks CTLA-4's docking station on T cells.
Allison was chair of the immunology program and director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center in New York. He started at MD Anderson on Nov. 1. He is a member of the National Academy of Sciences and the Institute of Medicine, as well as a fellow of the American Academy of Microbiology and the American Association for the Advancement of Science.
The AACR-CRI Lloyd J. Old Award in Cancer Immunology was established to recognize an active scientist whose outstanding and innovative research in cancer immunology has had a far-reaching impact on the cancer field. CRI is the world's only nonprofit organization dedicated exclusively to harnessing the immune system's power to conquer cancer.
Old was scientific director of CRI for 40 years and also a researcher at Memorial Sloan-Kettering Cancer Center and the Ludwig Institute for Cancer Research in New York.
The AACR also announced the electronic launch of its newest journal, Cancer Immunology Research, which will publish original articles on major advances in cancer immunology. A print preview issue was distributed at the annual meeting.
AACR is the world's first and largest professional organization dedicated to advancing cancer research. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates in more than 90 countries. About 18,000 people attended the 2013 annual meeting.