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

• Main Authors: Jiali Cheng, Lei Zhao, Yuanyuan Zhang, Yun Qin, Yuqi Guan, Tong Zhang, Chaohong Liu, Jianfeng Zhou
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-11-01
• Series: Frontiers in Oncology
• Subjects: CAR T-cell therapy; resistance mechanism; T-cell defect; tumor factor; tumor microenvironment
• Online Access: https://www.frontiersin.org/article/10.3389/fonc.2019.01237/full

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, problems of resistance and relapse are starting to be 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 for improving CAR T-cell therapy.