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Imaging CAR T Cells with a Dual Function PET Reporter Gene

Michael D. Farwell, MD

Dr. Farwell is an assistant professor in the Department of Radiology at the University of Pennsylvania in Philadelphia. His SU2C Innovative Research Grant project, awarded in 2017, is titled “Imaging CAR T Cells with a Dual Function PET Reporter Gene.”

Immunotherapy has brought a sea change to how cancers are treated, with the potential for complete recovery from cancers with otherwise low survival rates. Among those therapies, CAR T-cell therapy has shown dramatic activity in several hematological cancers, including advanced, chemotherapy-resistant acute lymphoblastic leukemia. In CAR T cells, a type of white blood cell called T cells that scan the bloodstream for cellular abnormalities and infections have been engineered with chimeric antigen receptors (CARs) that target tumor-associated antigens. These CAR T cells have shown activity in a number of hematological cancers, however, a major obstacle in the development of CAR T cells that target solid tumors is the difficulty in determining the treatment efficacy and related toxicity because the fate of the therapeutically administered cells cannot be assessed directly. To address these issues, in vivo cell-tracking methods are critically needed to monitor noninvasively the fate of the administered cells in the body. To achieve this goal, Dr. Farwell proposes to develop a novel traceable genetic system that carries a potent “suicide gene.” With such a system, the fate of T cells will be monitored via a radiotracer using positron emission tomography (PET). Furthermore, the suicide gene function can be activated if the engineered T cells need to be destroyed because of undesirable and/or toxic effects. By developing such a tool, Dr. Farwell and his team have the potential to create a platform that opens the door to numerous imaging applications that will find widespread use in CAR T-cell therapy and other cell-based therapies.