结直肠癌中CAR-T细胞免疫治疗的研究现状及展望

Chimeric antigen receptor T cell immunotherapy for colorectal cancer:current status and prospects

嵌合抗原受体T(CAR-T)细胞免疫疗法是一种通过基因工程修饰来招募T细胞对抗肿瘤的新方法。CAR-T细胞免疫疗法在血液系统恶性肿瘤中已取得巨大的进展,因此,许多研究者提出将其用于诸如结直肠癌(CRC)这类实体肿瘤。但是,由于肿瘤特异抗原的缺乏,肿瘤细胞间的紧密连接和免疫抑制性的肿瘤微环境,以及治疗不良反应等问题,限制了CAR-T细胞疗法在CRC的应用。为克服实体瘤免疫治疗的这些困境,研究人员提出了多种优化CAR的治疗策略,这些策略各有其优势和不足,本文总结了CRC中CAR-T细胞免疫疗法的靶点选择,治疗不良反应和相应的优化策略等现状,并提出对实体瘤CAR-T细胞免疫治疗的未来展望。

Chimeric antigen receptor T(CAR-T)cell immunotherapy is a novel method that is genetically engineered to recruit T cells against malignant disease.Application of CAR-T cell immunotherapy has made great progress in hematological malignancies,hence,it has been proposed for solid tumors like colorectal cancer(CRC)by many researchers.However,the efficacy and application of this method in CRC are limited for the intrinsic challenges posed to CAR-T cells,including the lack of tumor-specific antigens,the tight connection of tumor cells,and unfavorable tumor microenvironment,as well as the side effects.New approaches are proposed to overcome the multiple challenges to alleviate the difficult situation of CAR-T cells in CRC,each of which has its advantages and disadvantages.In this review,we sum up the current stage of knowledge about target-selection,adverse events,the tumor microenvironment and corresponding optimization strategies,and the future prospect of CAR-T cell immunotherapy for solid tumors is also presented.