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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01237

Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies

  • 1Department of Hematology, Tongji Hospital, China
  • 2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
  • 3Tongji Medical College, Huazhong University of Science and Technology, China
  • 4School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, China

Taking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. The most representative in this respect, as well as the most successful example, is CD19 CAR T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL). However, with the widespread use of CAR T-cell therapy, the problems of resistance and relapse are being gradually considered. This review provides a comprehensive picture of the mechanisms of resistance to CAR T-cell therapy from three aspects, namely, CAR T-cell factors, tumor factors and tumor microenvironment factors, offering insights to improve CAR T-cell therapy.

Keywords: CAR T-cell therapy, Resistance mechanism, T-cell defect, Tumor factors, Tumor Microenvironment

Received: 02 Apr 2019; Accepted: 28 Oct 2019.

Copyright: © 2019 Cheng, Zhao, Zhang, Qin, Guang, Zhang, Liu and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jianfeng Zhou, Department of Hematology, Tongji Hospital, Wuhan, China, jfzhou@tjh.tjmu.edu.cn