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FINDING CURES TOGETHER<sup>SM</sup>

SU2C-CRI Dream Team: Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy

Leaders

James P. Allison, PhD

James P. Allison, PhD
Chairman, Department of Immunology, The University of Texas MD Anderson Cancer Center

Antoni Ribas, MD, PhD

Antoni Ribas, MD, PhD
Director of the Tumor Immunology Program Area, UCLA Jonsson Comprehensive Cancer Center

Co-leaders

Drew M. Pardoll, MD, PhD

Drew M. Pardoll, MD, PhD
Director of the Division of Immunology and Abeloff Professor in the Departments of Oncology, Medicine, Pathology, and Molecular Biology and Genetics, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University

Cassian Yee, MD

Cassian Yee, MD
Professor, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center

Overview

Cancer immunotherapy is based on getting a patient's own immune system to attack their cancer. This Dream Team worked on two cancer immunotherapy approaches. In one approach, the Team used drugs called checkpoint inhibitors to foil the "tricks" that cancers rely on to escape natural immune cell attack. In the other approach, known as adoptive cell transfer (ACT), the Team took patients' own immune cells to the lab, made these cells into more efficient cancer-killing "armies," and returned the cells to the patient.

Work by members of this Dream Team contributed to the FDA approval of two new checkpoint inhibitors, pembrolizumab and nivolumab. The Team analyzed tumor samples to determine how checkpoint inhibitors work and to identify biomarkers, molecules that can be measured in patients' blood, tumor samples, or other biological specimens, that can predict which patients will respond to immune therapy.

Progress to Date

The Team is pursuing multiple ways to make better T-lymphocytes for ACT. They are testing which antigen "flags" are expressed by tumor cells to find out how best to target the T-lymphocyte attack, and whether they can personalize immune-therapy to the "flags" present on individual patients' tumors. In some studies, they are isolating small numbers of T lymphocytes with the desired ability to recognize and kill cancer, expanding their numbers in the laboratory, and then giving them back to the patient. Alternatively, they are using gene transfer techniques to take the antigen-recognizing TCR from one T lymphocyte that is cancer-specific and insert it into many other T lymphocytes so that they then become cancer-specific. The Dream Team is also using artificial receptors based on antibodies, termed chimeric antigen receptors (CAR), to redirect the killing ability of T cells and restrict it to cancer cells.

Amount Of Funding:

$10 million

Principals

Glenn Dranoff, MD, Dana-Farber Cancer Institute, Boston, Mass.
Philip D. Greenberg, M.D., Fred Hutchinson Cancer Research Center, Seattle, Wash.

James R. Heath, PhD, California Institute of Technology (CalTech)
Michel Sadelain, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Ton Schumacher, PhD, Netherlands Cancer Institute, Amsterdam, The Netherlands
Jedd D. Wolchok, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York, N.Y.

Advocates

​Robert Behrens
Debra Black
Roy Doumani
Valerie Guild
Jonathan W. Simons
Mary Elizabeth Williams