嵌合抗原受体T细胞疗法在结直肠癌中的研究进展

Advances of CAR-T cell therapy in treating colorectal cancer

全球范围内,结直肠癌(colorectal cancer, CRC)是第三大常见的恶性肿瘤和癌症相关死亡的第二大原因。据世界卫生组织统计,全球每年新增超过190万例CRC患者,每年大约90万人死于结肠或直肠癌。近年来,嵌合抗原受体T(chimeric antigen receptor T, CAR-T)细胞疗法在部分血液肿瘤的治疗中取得了临床成功,更多靶向治疗CRC等实体瘤的CAR-T细胞疗法也正在陆续开发中。目前针对癌胚抗原(carcinoembryonic antigen, CEA)、自然杀伤细胞受体2D配体(natural killer group 2, member D ligand, NKG2DL)等靶点的CAR-T细胞疗法已经在临床试验中取得了显著效果,但同时也面临一些困境。本文总结了目前CAR-T细胞疗法治疗CRC的有效靶点的最新信息及其在临床试验或临床前研究的相关进展。同时,本文介绍了CAR-T细胞疗法在治疗CRC时面临的挑战(包括缺乏肿瘤特异性抗原、细胞因子释放综合征、不利的肿瘤微环境以及CAR-T细胞浸润程度低等)。综上所述,本文总结了CAR-T细胞疗法治疗CRC的最新研究进展及挑战,以期为CRC的临床治疗提供新思路。

Globally,colorectal cancer(CRC)ranks as the third most common cancer and the second leading cause of cancer-related fatalities.According to the World Health Organization,there are over 1.9 million annual cases of CRC diagnosed worldwide,resulting in more than 900000 deaths.In recent years,chimeric antigen receptor T(CAR-T)cell therapy has shown clinical success in treating certain hematological malignancies and is now being explored for its potential in targeting solid tumors like CRC.Currently,CAR-T cell therapies targeting carcinoembryonic antigen(CEA),natural killer group 2,member D ligand(NKG2DL),and other markers have achieved remarkable results in clinical trials,albeit encountering significant challenges.This review summarizes the promising targets of CAR-T cell therapy for CRC and highlights progress made in clinical trials and preclinical studies.Additionally,the review discusses the challenges faced by CAR-T cell therapy in CRC treatment,including a shortage of tumor-specific antigens,cytokine release syndrome,adverse tumor microenvironment,and limited infiltration of CAR-T cells.In summary,this review provides an overview of the latest research progress and challenges in CAR-T cell therapy for CRC,aiming to contribute fresh insights for the clinical treatment of this disease.