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Review
. 2021 Apr 6;11(4):69.
doi: 10.1038/s41408-021-00459-7.

CAR-T cell therapy: current limitations and potential strategies

Robert C Sterner  1 , Rosalie M Sterner  2
Affiliations
Review

CAR-T cell therapy: current limitations and potential strategies

Robert C Sterner et al. Blood Cancer J. .

Abstract

Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.

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Conflict of interest statement

R.M.S. is an inventor on patents related to CAR-T cell therapy licensed to Humanigen through Mayo Clinic.

Figures

Fig. 1
Fig. 1. Limitations of CAR-T Cell Therapy.
Current challenges in CAR-T cell therapy include (A) antigen escape, (B) on-target off-tumor effects, (C) trafficking and infiltration of tumors, (D) the immunosuppressive tumor microenvironment, and (E) CAR-T cell-associated toxicities.
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