George Coukos, M.D., Ph.D.
University of Pennsylvania Medical Center
Engineering T cells to Augment Natural Immunity for Ovarian Cancer
Project Summary
A major problem for the immune system is that it has difficulty killing tumor cells because the receptors that bind the immune cells to the tumor cells have weak interactions. During the first year of this program project we have engineered a panel of molecules that bind much more tightly to tumor cells. The engineered molecules have been inserted into immune cells, and the immune cells are able to kill tumor cells much more efficiently than immune cells that express the natural receptors for tumor cells. These molecules are either modified T cell receptors or recombinant chimeric immunoreceptors directed against tumor cells or tumor endothelial cells. Project 1 develops modified T cell receptors while project 2 develops chimeric immunoreceptors against tumor cells. Both projects have made substantial progress. In an initial experiment, mice with progressive tumors that resemble advanced ovarian cancer were cured by a single injected of the immune cells engineered with modified T Cell receptor. In project 2 the function of chimeric immunoreceptors has been demonstrated in vitro. Progress during the first year has been rapid in both projects and there have been no obstacles that prevent the project from moving forward to the next stage of experiments that will more definitively establish the antitumor potential of the engineered immune cells. Project 3 has met substantial technical difficulties which we are however on our way to solve. The significance of these experiments are that they could enable the testing of a new form of cell therapy using engineered immune cells that could have potent antitumor effects in women with advanced ovarian cancer.
Bio
George Coukos, M.D., Ph.D., is a tenured Associate Professor in the Division of Gynecologic Oncology and also directs the Gynecologic Malignancy Research Program at the University of Pennsylvania. Dr. Coukos also serves as Director of Gynecology Service at the Veteran’s Administration Hospital in Philadelphia. In 2005, Dr. Coukos was appointed the Celso Ramon Garcia Chair in Reproductive Biology, and, in 2007, the Center for Research on the Early Detection and Cure for Ovarian Cancer was established with Dr. Coukos as its Director.
Dr. Coukos is best known for his effort and contributions in translational research on understanding the immune system’s response to ovarian cancer. Dr. Coukos’ findings provide the first proof that a spontaneous immune response against the tumor dramatically impacts the clinical course of ovarian cancer. His current research interests focus on three areas that revolve around the overarching theme of the tumor microenvironment: tumor immune surveillance and tolerance; immune-vascular interactions; and microenvironment editing by tumor cells. Dr. Coukos is currently involved in preclinical research focused on the development and optimization of combinatorial biological therapies and is involved in clinical trials testing immune therapies against ovarian cancer.
He earned an M.D. (cum laude) from the University of Modena in Italy and a Ph.D. in Reproductive Biology from the University of Patras School of Medicine in Greece. He completed his Obstetrics and Gynecology residency and a clinical fellowship in Gynecologic Oncology at the University of Pennsylvania and is board-certified in both.
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