A Metabolism Toolbox for CAR T Therapy

A Metabolism Toolbox for CAR T Therapy Xuequn Xu†, J. N. Rashida Gnanaprakasam†, John Sherman† and Ruoning Wang* Center for Childhood Cancer and Blood Diseases, Hematology/Oncology & BMT, The Research Institute at Nationwide Children's Hospital, Ohio State University, Columbus, OH, United States The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) through genetic engineering is one of the most promising new therapies for treating cancer patients. A robust CAR T cell-mediated anti-tumor response requires the coordination of nutrient and energy supplies with CAR T cell expansion and function. However, the high metabolic demands of tumor cells compromise the function of CAR T cells by competing for nutrients within the tumor microenvironment (TME). To substantially improve clinical outcomes of CAR T immunotherapy while treating solid tumors, it is essential to metabolically prepare CAR T cells to overcome the metabolic barriers imposed by the TME. In this review, we discuss a potential metabolism toolbox to improve the metabolic fitness of CAR T cells and maximize the efficacy of CAR T therapy. Cancer Cell Metabolic Program Since cancer cells must constantly proliferate, they must also continuously generate new biomass. This in turn requires a substantially different metabolic program than that of non-proliferating somatic cells. Most non-proliferating cells utilize oxidative phosphorylation (OXPHO...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research