CAR-T细胞疗法传统领域的前沿进展

Advances in the Traditional Field of CAR-T Cell Therapy

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。

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.