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Enhancing CAR T-cell therapies against solid tumors: Mechanisms and reversion of resistance

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1053120

Keywords

CAR T-cell; solid tumor; antigen viability; microenvironment; tumor infitration; combined therapy

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Chimeric antigen receptor (CAR) T-cell therapy is a treatment that enhances tumor-specific killing using engineered immunoreceptors. While new generations of CAR T-cell therapies have significantly improved efficacy in leukemia cases, only a few therapies have gained FDA approval and are applied to hematologic cancers. Targeting solid tumors through CAR T-cell therapies still faces several challenges, but recent advances have provided new insights and potential reversal therapies.
Chimeric antigen receptor (CAR) T-cell therapy, belonging to adoptive immune cells therapy, utilizes engineered immunoreceptors to enhance tumor-specific killing. By now new generations of CAR T-cell therapies dramatically promote the effectiveness and robustness in leukemia cases. However, only a few CAR T-cell therapies gain FDA approval till now, which are applied to hematologic cancers. Targeting solid tumors through CAR T-cell therapies still faces many problems, such as tumor heterogeneity, antigen loss, infiltration inability and immunosuppressive micro-environment. Recent advances provide new insights about the mechanisms of CAR T-cell therapy resistance and give rise to potential reversal therapies. In this review, we mainly introduce existing barriers when treating solid tumors with CAR T-cells and discuss the methods to overcome these challenges.

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