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Review 10.1172/JCI142030

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

Emiliano Roselli,1 Rawan Faramand,2 and Marco L. Davila1,2,3,4

1Department of Clinical Science, and

2Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.

4Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

Find articles by Roselli, E. in: JCI | PubMed | Google Scholar |

1Department of Clinical Science, and

2Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.

4Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

Find articles by Faramand, R. in: JCI | PubMed | Google Scholar

1Department of Clinical Science, and

2Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

3Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.

4Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

Find articles by Davila, M. in: JCI | PubMed | Google Scholar |

Published January 19, 2021 - More info

Published in Volume 131, Issue 2 on January 19, 2021
J Clin Invest. 2021;131(2):e142030. https://doi.org/10.1172/JCI142030.
© 2021 American Society for Clinical Investigation
Published January 19, 2021 - Version history
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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.

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