CAR T cells mediate antitumor effects in a small subset of cancer patients 1-3 , but dysfunction due to T cell exhaustion is an important barrier to progress 4-6. To investigate the biology of exhaustion in human T cells expressing CAR receptors, we used a model system employing a tonically signaling CAR, which induces hallmark features of exhaustion 6. Exhaustion was associated with a profound defect in IL-2 production alongside increased chromatin accessibility of AP-1 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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are coinventors on a patent application for a CD93-CAR. C.L.M. is a cofounder and consultant for Lyell Immunopharma, and Syncopation Life Sciences, which are developing CAR-based therapies, and serves as an advisor and consultant for Roche, NeoImmune Tech, Immatics, Apricity and Nektar. R.G.M. is a cofounder of Syncopation. E.S. is a consultant for Lyell Immunopharma. R.G.M. is a consultant for Lyell Immunopharma, Gamma Delta Therapeutics, Zai Lab, and Aptorum Group. R.M. is on the Board of Directors of BeyondSpring Inc, on the Scientific Advisory Boards of Kodikaz Therapeutic Solutions Inc., Coherus Biosciences, and Zenshine Pharmaceuticals, and is an inventor on a number of patents related to CD47 cancer immunotherapy licensed to Gilead Sciences, Inc. K.R.P., A.T.S., and HYC are cofounders of Cartography Biosciences. A.T.S is a scientific founder of Immunai and receives research funding from Arsenal Biosciences. H.Y.C is a cofounder of Accent Therapeutics and Boundless Bio, and an advisor to 10X Genomics, Arsenal Biosciences, and Spring Discovery. The remaining authors declare no competing financial interests.