James P. Allison

The University of Texas MD Anderson Cancer Center, Houston, USA

Professor and Chair, Department of Immunology
Executive Director, Immunotherapy Platform
Deputy Director, David H. Koch Center for Applied Research for Genitourinary Cancers
Associate Director, CCIR
Joined MD Anderson Cancer Center: November 2012

Research Interests
Dr. Allison’s pioneer work has transformed the fields of basic and tumour immunology. Early in his career, he identified and characterized key molecules involved in T-cell activation, including the T-cell receptor (TCR), the prototypical costimulatory receptor CD28 and coinhibitory receptor CTLA-4, providing evidence that T-cell responses are determined by a complex process involving antigen driven TCR signalling plus integration of costimulatory and coinhbitory signals. His landmark translation studies showing antibody-mediated blockade of CTLA-4 co-inhibitory function could enhance antitumor immunity and result in tumour rejection in mice prompted clinical development of ipilimumab, a CTLA-4 blocking monoclonal antibody. Ipilimumab is the first drug of its kind to show survival benefit in melanoma patients and was approved by the FDA in 2011 as a standard-of-care therapy for late-stage melanoma patients. Dr. Allison’s concept of antibody-mediated blockade of immunologic checkpoints as cancer therapy has opened a new field of immunotherapy, with second-generation agents, such as anti-PD-1 antibodies, currently being investigated in pre-clinical and clinical settings as treatments for cancer.

Allison’s group continues to study basic mechanisms regulating T-cell responses and to interweave mouse and human studies to improve existing approaches and develop new strategies for manipulating T cell responses to cure cancer. Another major activity will be to build a team of clinicians and physician/scientists working together in a state-of-the-art immune monitoring facility to accelerate the movement of immune-based combinatorial therapies into clinical trials. These trials will not necessarily have conventional clinical endpoints, but will be designed to yield mechanistic data that would inform combinations and schedules likely to have clinical impact. These would be small trials, likely in the pre-surgical or neoadjuvant setting, with extensive collection and analysis of samples from tumour and local lymphoid tissues as well as peripheral blood. The overall goal of this immense project will be to dissect the immunologic impact of novel therapies and combinations as well as examining the tumour itself for alterations that may render the tumour resistant to specific mechanisms of immune attack.