Chairman, Immunology Program
University of Texas MD Anderson Cancer Center, Houston, TX
Motivation:
The Pezcoller Foundation-AACR International Award was established in 1997 to recognize a scientist who has made a major scientific discovery in basic cancer research, or who has made significant contributions to translational cancer research; who continues to be active in cancer research and has a record of recent and noteworthy publications; and whose ongoing work holds promise for continued substantive contributions to progress in the field of cancer.
This award honors James P. Allison, PhD, for his seminal discoveries that established new paradigms in basic cancer immunology and led to the development of novel cancer therapeutics. Specifically, he is recognized for his identification of CTLA-4 as an inhibitory receptor on T cells that serves as a checkpoint to ensure proper control of immune responses. He subsequently developed and tested the hypothesis that blockade of CTLA-4 would enhance anti-tumor T cell responses by releasing CTLA-4 suppression. The success of these studies opened the field of immune checkpoint blockade in human cancer therapy. Dr. Allison’s findings have had a profound impact on patients and revolutionized the way we think about cancer treatment.
Throughout his career, Dr. Allison has contributed significantly to the field of immunology. Early in his career, his laboratory provided several important insights into the basic mechanisms involved in T cell activation, T cell receptor structure, and antigen recognition. He also investigated other receptors that participated in regulation of T cell activation or inhibition; for example, the CD28 and CTLA-4 pair of T cell receptors was found to regulate dichotomous T cell responses when linked to their common binding protein, B7-1,2, on antigen presenting cells. Dr. Allison demonstrated that CD28 engagement stimulated T cell function, whereas CTLA-4 suppressed T cell activation. These studies and subsequent mechanistic investigations led Dr. Allison to propose that CTLA-4 inhibition of T cells limited immune destruction of tumor cells and that blockage of this receptor might unleash T cell anti-tumor activity.
He then established models to test this hypothesis, generating blocking monoclonal antibodies to CTLA-4 and showing that these antibodies induced tumor regression in mice. The success of these preclinical studies motivated Dr. Allison to work with Bristol-Myers Squibb to develop and test a therapeutic monoclonal anti-CTLA-4 antibody (ipilimumab) in cancer patients. Treatment with ipilimumab was shown to induce remission in a subset of patients, providing further evidence of efficacy in Phase II and III trials, and therefore led to FDA approval of the drug in 2011. These studies of CTLA-4 laid the foundation for development of a new class of “immune checkpoint therapies”, drugs that target T cell inhibitory pathways (e.g., Pembrolizumab for PD-1/PD-L1 blockade) and changed the landscape of cancer treatment.
Dr. Allison’s outstanding accomplishments have been recognized by his appointment as a Howard Hughes Medical Institute Investigator, his election to the National Academy of Sciences, the Institute of Medicine, the American Association of Arts and Sciences, the American Society of Microbiology, and as a Fellow of the AACR Academy. Likewise, he is the recipient of several prestigious awards such as the Canada Gairdner International Award, the 2013 Innovation Award for Bioscience, and two AACR awards, the AACR- Lloyd J. Old Award in Cancer Immunology and the AACR G.H.A. Clowes Memorial Award.
