CART细胞疗法传统领域的前沿进展

摘要/Abstract

摘要： 细胞治疗领域因其高度精准化和个性化的优势，已成为未来人类医学发展的热门方向。细胞治疗是指应用人的自体、同种异体或异种（非人体）的细胞，经体外操作后回输（或植入）人体的治疗方法。其中嵌合抗原受体T细胞免疫疗法（CART细胞疗法）是近几年兴起的过继性细胞免疫治疗，主要通过将嵌合抗原受体的特异性与T细胞的免疫作用相结合，再经过特异性识别对恶性肿瘤细胞进行杀伤。CART细胞疗法的传统领域主要是治疗血液恶性肿瘤，临床效果较好。目前，全球上市的CART细胞疗法产品共计7种。本研究梳理了CART细胞疗法的结构组成和发展历程，概述了全球上市的CART细胞疗法在血液肿瘤方面应用的前沿进展，探讨了CART细胞疗法当前面临的两大问题(毒副作用问题和复发率问题)；同时聚焦这些问题挑战分别给出了解决策略：通过改进CART细胞结构降低细胞毒性、通过调整给药策略降低剂量、通过常规药物治疗减小毒副作用和通过设计多靶向抗原CART细胞降低复发率；最后提出展望：通过设计开发有效、安全和低成本的CART细胞疗法，同时采用联合治疗和疾病监测方法，将CART细胞疗法的全部治疗潜力发挥出来，旨在为我国细胞疗法领域的专家学者提供参考。

关键词: font-size:medium, ">细胞治疗；嵌合抗原受体；CART；免疫疗法；血液肿瘤

Abstract: The field of cell therapy has become a hot direction for the future development of human medicine due to its advantages of high precision and personalization. Cell therapy refers to the therapy that use human autologous， allogeneic or xenogeneic (nonhuman) cells， after in vitro operation， and then infused into the human body (or implant to). Chimeric antigen receptor T cell immunotherapy (CART cell therapy) is adoptive cellular immunotherapy emerging in recent years， which mainly kills malignant tumor cells by combining the specificity of the chimeric antigen receptor with the immune effect of T cells， and then through specific recognition. The traditional field of CART cell therapy is mainly the treatment of hematological malignancies， and the clinical effect is better. Currently， there are 7 CART cell therapy products on the market worldwide. This study reviewed the composistion and development process of CART cell hematologic therapy， summarized the global listings CART cell therapy in the forward progress of the application of haemal tumor， discussed the CART cell therapy currently facing two big problems (side effects and the recurrence rate). At the same time， focusing on these problems and challenge， the resolution strategies were given respectively： the cytotoxicity can be reduced by improving the structure of CART cells， the dose can be reduced by adjusting the administration strategy， the toxicity and side effects can be reduced by conventional drug therapy， and the recurrence rate can be reduced by designing multitargeted antigen CART cells. Finally， the full therapeutic potential of CART cell therapy can be realized through the design and development of effective， safe， and lowcost CART cell therapies and combine with combination therapy and disease surveillance. It is hoped to provide a reference for Chinese experts and scholars in the field of cell therapy.

Key words: font-size:medium, ">Cell therapy； Chimeric antigen receptor； CART； Immunotherapy； Hematologic neoplasms

中图分类号:

李贺, 任嘉慧, 石颖慧, 周云乔, 秦瑜, 王铁山. CART细胞疗法传统领域的前沿进展[J]. 中国医药导刊, 2022, 24(10): 966-973.

LI He, REN Jiahui, SHI Yonghui, ZHOU Yunqiao, QIN Yu, WANG Tieshan. Advances in the Traditional Field of CART Cell Therapy[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2022, 24(10): 966-973.

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