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Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies
Jiali Cheng (Tongji Hospital, Huazhong University of Science and Technology), Lei Zhao (Tongji Hospital, Huazhong University of Science and Technology), Yuanyuan Zhang (Tongji Hospital, Huazhong University of Science and Technology), Yun Qin (Tongji Hospital, Huazhong University of Science and Technology), Yuqi Guan (Tongji Hospital, Huazhong University of Science and Technology), Tong Zhang (Huazhong University of Science and Technology), Chaohong Liu (Huazhong University of Science and Technology), Jianfeng Zhou (Tongji Hospital, Huazhong University of Science and Technology)
Résumé : 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.