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嵌合抗原受体T细胞(CAR-T)疗法治疗实体瘤的当前挑战与治疗进展

Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors.

作者信息

Chen Tong, Wang Mingzhao, Chen Yanchao, Liu Yutao

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

出版信息

Cancer Cell Int. 2024 Apr 15;24(1):133. doi: 10.1186/s12935-024-03315-3.

Abstract

The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors.

摘要

嵌合抗原受体(CAR)T细胞在血液系统恶性肿瘤治疗中的应用已成为一项值得关注的治疗突破。然而,CAR-T细胞疗法在实体瘤中的应用和有效性仍然有限,主要原因是缺乏肿瘤特异性靶抗原、存在免疫抑制性肿瘤微环境、T细胞浸润和增殖受限以及出现严重毒性。本综述探讨了CAR-T的历史及其在实体瘤治疗中的最新进展。根据最近的研究,优化CAR-T细胞的设计、应用逻辑门控CAR-T细胞以及改进治疗药物的递送方法都可以提高CAR-T细胞疗法的疗效。此外,联合疗法有望提高CAR-T细胞疗法的有效性。目前,许多涉及CAR-T细胞治疗实体瘤的临床试验正在积极进行。总之,CAR-T细胞疗法在治疗实体瘤方面既有潜力也有挑战。随着CAR-T细胞疗法的不断发展,将设计出进一步的创新方法来克服与这种治疗方式相关的挑战,最终为实体瘤患者带来更强的治疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cab8/11017638/ef1a7b97abd1/12935_2024_3315_Fig1_HTML.jpg

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