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Insight into next-generation CAR therapeutics: designing CAR T cells to improve clinical outcomes
Emiliano Roselli, … , Rawan Faramand, Marco L. Davila
Emiliano Roselli, … , Rawan Faramand, Marco L. Davila
Published January 19, 2021
Citation Information: J Clin Invest. 2021;131(2):e142030. https://doi.org/10.1172/JCI142030.
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Review

Insight into next-generation CAR therapeutics: designing CAR T cells to improve clinical outcomes

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Abstract

Chimeric antigen receptor (CAR) T cell therapy has shown considerable promise for hematologic malignancies, leading to the US Food and Drug Administration approval of two CAR T cell–based therapies for the treatment of B cell acute lymphoblastic leukemia and large B cell lymphoma. Despite success in hematologic malignancies, the treatment landscape of CAR T cell therapy for solid tumors has been limited. There are unique challenges in the development of novel CAR T cell therapies to improve both safety and efficacy. Improved understanding of the immunosuppressive tumor microenvironment and resistance mechanisms has led to encouraging approaches to mitigating these obstacles. This Review will characterize challenges with current CAR T designs for hematologic malignancies and solid tumors and emphasize preclinical and clinical strategies to overcome them with novel CAR T cell therapies.

Authors

Emiliano Roselli, Rawan Faramand, Marco L. Davila

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Figure 1

Structure and evolution of CARs.

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Structure and evolution of CARs.
CARs are composed of an antigen-recogni...
CARs are composed of an antigen-recognition domain (mainly scFv of monoclonal antibodies) fused to a hinge/transmembrane domain and intracellular signaling domains able to transduce activation signals to CAR T cells. Modification in the intracellular domains gave rise to a different generation of CAR T cells from the first generation, which included a CD3ζ motif, to the second and third generations, which included one or two costimulatory domains, respectively. VH, variable heavy chain; VL, variable light chain.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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