关键词: 嵌合抗原受体T细胞治疗, 缺氧敏感, 肿瘤微环境, 实体瘤

Abstract:

Chimeric antigen receptor T (CAR-T) cell therapy, as a kind of tumor immunotherapy, has made remarkable achievements for the treatment of hematological malignancy. Disappointingly, regarding solid tumors, CAR-T cells generally target tumor-associated antigens that are also widely expressed in normal tissues because of the lack of tumor specific antigen, resulting in on-target off-tumor effects, which may even endanger patients’ lives. Measures should be taken to overcome the off-target effects which severely limit the application of CAR-T cell therapy in solid tumors. A feasible strategy is to design hypoxia-sensitive CAR-T cells, which express CAR only in the hypoxic tumor microenvironment. Therefore, the redundant “accidental injury” can be avoided. In this review, common approaches as well as recent advances in the construction of hypoxia-sensitive CAR-T cells were discussed and summarized, which has guiding significance for enhancing the safety of CAR-T cell therapy and promoting the application of CAR-T cell in solid tumors.

Key words: Chimeric antigen receptor T cell therapy, Hypoxia-sensitive, Tumor microenvironment, Solid tumor