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


ABSTRACT: 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.

SUBMITTER: Cheng J 

PROVIDER: S-EPMC6882288 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Cheng Jiali J   Zhao Lei L   Zhang Yuanyuan Y   Qin Yun Y   Guan Yuqi Y   Zhang Tong T   Liu Chaohong C   Zhou Jianfeng J  

Frontiers in oncology 20191121


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, wit  ...[more]

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