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

摘要:

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。

Abstract:

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 900 000 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.