Current challenges and optimization strategies for CAR-T cell therapy for solid tumors
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摘要: 近年来,嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)疗法在血液肿瘤治疗中取得了突破性进展。然而,由于实体瘤异于血液肿瘤的特性,CAR-T在实体瘤治疗中并未取得很好的疗效。限制CAR-T疗效的关键因素主要包括实体瘤细胞本身及其特殊的肿瘤微环境(tumor microenvironment,TME)两方面,在CAR-T向肿瘤组织部位浸润、CAR-T在TME中维持抗肿瘤活性以及CAR-T对肿瘤细胞的靶向性识别杀伤等多个过程中损害CAR-T功能。为了解决这些问题,越来越多的临床前研究提出了潜在有效的解决办法,相应的临床研究也相继开展。本文将对CAR-T细胞治疗实体瘤的现存挑战及相应的优化策略进行综述,以期为CAR-T疗法的未来探索提供参考。Abstract: The sequential launch of chimeric antigen receptor T-cell (CAR-T cell) therapy products caused a breakthrough in the treatment of hematological tumors. However, owing to the differences in properties between solid tumors and hematological tumors, CAR-T cell shave not been used much in the treatment of solid tumors. Solid tumor cells themselves and their distinctive tumor microenvironment (TME) are two crucial factors limiting the efficacy of CAR-T cells by impairing their function in multiple processes, including their infiltration into the tumor site, maintenance of their anti-antitumor activity in the TME, and targeted recognition killing of tumor cells. To address these problems, an increasing number of preclinical studies have proposed potential effective solutions, and corresponding clinical studies also have been carried out. This manuscript focuses on reviewing the existing challenges and corresponding optimization strategies for CAR-T cells in solid tumor treatment, aiming to provide a reference for future exploration of its applications.
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