Clinical lessons learned from the first leg of the CAR T cell journey

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Chimeric antigen receptor (CAR) T cell therapy for B cell malignancies has surpassed expectations, driving an ever-expanding number of clinical trials and the first US Food and Drug Administration approvals of cell therapies for the treatment of cancer. This experience has illuminated some generalizable requirements for CAR T cell efficacy as well as the interplay between disease biology and clinical outcomes. Major CAR intrinsic variables affecting T cell behavior have been defined, and mechanisms of tumor resistance are increasingly understood. Here, we review the clinical experience with CAR T cells amassed to date, including but not limited to B cell malignancies, emphasizing factors associated with efficacy, resistance and major barriers to success. We also discuss how these insights are driving next-generation clinical trials, including those in solid tumors.

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Fig. 1: Patterns of failure after CD19-CAR T cell therapy and potential causes.

Debbie Maizels/Springer Nature

Fig. 2: Overcoming obstacles to enhance CAR T cell efficacy.

Debbie Maizels/Springer Nature


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Correspondence to Crystal L. Mackall.

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Peer review information: Hannah Stower was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Majzner, R.G., Mackall, C.L. Clinical lessons learned from the first leg of the CAR T cell journey. Nat Med 25, 1341–1355 (2019) doi:10.1038/s41591-019-0564-6

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