CAR-T细胞免疫疗法最新研究进展

Recent Advances in CAR-T Cell Immunotherapy

近年来,随着肿瘤免疫治疗研究的突飞猛进,嵌合抗原受体T细胞疗法作为现阶段最有发展前景的免疫疗法,以非主要组织相容性复合体限制的方式识别、鉴别并靶向抗原,通过激活信号转染到T细胞中使它们具有特异性识别和杀伤肿瘤的能力。由于它们同时具有靶向性、杀伤活性和持久性等特点,因此在血液恶性肿瘤的治疗中凸显出巨大优势。随着嵌合抗原受体T细胞(CAR-T)技术的发展并在B细胞肿瘤中取得显著疗效,人们把目光投入更多的实体瘤与血液肿瘤靶点中。免疫治疗靶向策略旨在找到针对相应肿瘤细胞的特异性抗原,并针对该抗原设计CAR-T细胞。CD19 CAR-T细胞已经在70%~90%的急性淋巴细胞白血病患者中显示出完全和持久的缓解作用。但在获得显著疗效的同时,也存在着脱靶效应、神经毒性以及细胞因子风暴等问题。文章主要就CAR-T技术概况、抗肿瘤机制及在血液系统恶性肿瘤治疗中的进展,以及其安全性等方面进行综述。

In recent years,with the rapid advancement of tumor immunotherapy,chimeric antigen receptor T cell therapy is the most promising immunotherapy at this stage,identifying and targeting antigens in a manner that is not restricted by major histocompatibility complexes. Transfection into T cells by activation signals gives them the ability to specifically recognize and kill tumors. Because of their simultaneous targeting,killing activity and persistence,they have great advantages in the treatment of hematological malignancies. With the development of chimeric antigen receptor T cell( CAR-T) technique and significant efficacy in B cell tumors,people have turned their attention to more solid tumors and blood tumor targets. The immunotherapeutic targeting strategy aims to find specific antigens for the corresponding tumor cells and to design CAR-T cells against the antigen. CD19 CAR-T cells have shown complete and lasting remission in 70%-90% of patients with acute lymphoblastic leukemia. However,while achieving significant therapeutic effects,there are also problems such as off-target effects,neurotoxicity,and cytokine storms. This article reviews the general situation of CAR-T technique,anti-tumor mechanism and progress in the treatment of hematological malignancies,as well as its safety.