摘要: |
胃癌是最常见的恶性肿瘤之一,当前我国胃癌就诊患者仍以进展期为主,晚期患者就诊时多已失去手术治疗的机会,而传统的放疗、化疗和靶向治疗效果并不理想。嵌合抗原受体(CAR)-T细胞(CAR-T)免疫疗法作为一种新的治疗手段,在血液系统恶性肿瘤中疗效显著,也为胃癌的免疫治疗开辟了新途径。然而,由于胃癌的异质性、肿瘤微环境免疫抑制、肿瘤靶抗原逃逸及脱靶毒性等问题,使得CAR-T免疫疗法在胃癌治疗中的应用存在挑战。本文综述了CAR的结构及CAR-T治疗原理、CAR-T治疗晚期胃癌的主要靶点及治疗现状,并探讨了CAR-T治疗胃癌面临的挑战,旨在为晚期胃癌的临床免疫治疗提供新思路。 |
关键词: 胃肿瘤 免疫疗法 嵌合抗原受体T细胞 密封蛋白18.2 自然杀伤细胞活化型受体 上皮细胞黏附分子 |
DOI:10.16781/j.CN31-2187/R.20230501 |
投稿时间:2023-09-03修订日期:2024-01-18 |
基金项目:国家自然科学基金面上项目(81372048). |
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Chimeric antigen receptor T cell immunotherapy in advanced gastric cancer: research progress |
WANG Hao,LI Zhengxing,LUO Tianhang* |
(Department of Gastrointestinal Surgery, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China *Corresponding author) |
Abstract: |
Gastric cancer (GC) is one of the most common malignant tumors, and most GC patients in China are diagnosed as progressive GC at their first visit and late stage patients fail to have surgical treatment. The effects of conventional treatments, including chemotherapy, radiotherapy and targeted therapy, are limited and may induce poor prognosis. As a new treatment in hematological malignancy, chimeric antigen receptor (CAR)-T cell (CAR-T) immunotherapy is indicated as a promising treatment for advanced GC, which paves a new way for the GC immunotherapy. However, there are still some obstacles to overcome, such as the heterogeneity of GC, immunosuppression of tumor microenvironment, tumor target antigen escape and off-target toxicity. In this review, the CAR structure, therapeutic principle of CAR-T, and the main targets and treatment status of CAR-T immunotherapy for advanced GC are reviewed; the challenges faced by CAR-T immunotherapy in GC are discussed, so as to provide new ideas for the clinical immunotherapy of advanced GC. |
Key words: stomach neoplasms immunotherapy chimeric antigen receptor T cell claudin 18.2 natural killer cell group 2 member D epithelial cell adhesion molecule |