Researcher slated to lead immunology translational research Dream Team
Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) have formed a Dream Team project dedicated to cancer immunology to be led by James P Allison, chair of the Department of Immunology, director of the Immunotherapy Platform, Co-Director of the David H. Koch Center for Applied Research of Genitourinary Cancers of the Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center.
The Dream Team will receive up to $10 million in funding over three years to apply recent advances in immunology to laboratory and clinical efforts aimed at making marked progress in the treatment, control and prevention of cancer. Allison's pioneering work on the basic biology of immune system T cells has been broadly applied to a variety of cancers and has been indispensable to the definitive progress being made against these diseases.
"For decades investigators have sought to mobilize a patient's immune system to attack their cancer. This is a compelling approach to cancer therapy because of the immune system's special properties," said Allison. "The immune system has the ability to provide long-lived memory, adapt to changes in the tumour and recognize cancer antigens with exquisite specificity regardless of tumour type."
According to Allison, scientific and clinical discoveries of the last few years have the potential to rapidly impact the field of immunology, which has had limited clinical success to date. Specifically, the Dream Team will advance two converging findings:
Inhibitory checkpoints are molecules that disable T lymphocytes in the immune system from killing cancer cells. Research has found that blocking these checkpoints - a concept known as checkpoint blockade - can lead to anti-tumour immune responses and clinically significant results in patients. Dream Team members will explore how checkpoints such as CTLA-4 and PD-1 can be exploited - targeted in combination, or used in combination with other therapies - to increase therapeutic efficacy.
Engineered T cells generated from a cancer patient's tumour can be returned to a patient to target cancer cells in a process described as adoptive cell transfer (ACT). Building on past studies showing ACT to result in durable clinical responses, the team will pursue multiple strategies to "re-educate" T cells to seek and destroy cancerous tumours.
"The goal is to expand and explore combinations of these two new therapies. Ultimately, we expect to optimize these uniquely successful and complementary approaches, and achieve durable responses in a large fraction of patients suffering from a variety of types of cancer," said Allison.
Allison joined MD Anderson in November 2012. Most recently, discoveries from his lab led to the first drug - an anti-CTLA-4 antibody - to improve the survival rate of patients with metastatic melanoma by five years or longer. The Stand Up to Cancer Dream Team, in addition to leading the Immunotherapy Platform and incorporating it into the Moon Shot Program, are among his first projects at the institution.
MD Anderson researchers are involved with other Stand Up to Cancer Dream Teams, including those investigating epigenetics, the PI3K pathway and circulating tumour cells. The "Immune Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy" project is estimated to start in March, with the first clinical trials scheduled to open in early 2014. It is the eighth Dream Team created by Stand Up to Cancer since the programme's inception in 2008.
Joining Allison as co-leader is Antoni Ribas, professor of medicine, surgery, and molecular and medical pharmacology, director of the tumour immunology programme area at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (UCLA). Allison plans to collaborate with MD Anderson's Padmanee Sharma, Associate Professor, Department of Genitourinary Medical Oncology, and Patrick Hwu, professor and chair, Department of Melanoma Medical Oncology on this research. Drs. Sharma and Hwu will serve as Co-Directors of the Immunotherapy Platform at MD Anderson.
"This Dream Team brings together a group of people who have made incredible contributions to the world of immunotherapy," said Allison. "For the first time we will be joined in our research to concentrate on this important goal."
Dr. Allison will also collaborate with Lynda Chin, M.D., Professor and Chair of Genomic Medicine; Louis Pisters, M.D., Professor of Urology; Patricia Troncoso, M.D., Professor of Pathology; Christopher Wood, M.D., Professor of Urology; Peter Thall, Ph.D., Professor of Biostatistics; Surena Matin, M.D., Associate Professor of Urology; John Ward, M.D., Associate Professor of Urology; Ana Aparicio, M.D., Assistant Professor of Genitourinary Medical Oncology, and Priya Rao, M.D., Assistant Professor of Pathology. These collaborations will bring together a multidisciplinary approach to accomplish the goals of the Stand Up to Cancer Grant. In addition to MD Anderson and UCLA, the Dream Team scientists represent six institutions including Johns Hopkins University, Fred Hutchinson Cancer Research Center, Dana-Farber Cancer Institute, California Institute of Technology, Memorial Sloan-Kettering Cancer Center, and the Netherlands Cancer Institute.