CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer.
CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer.
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嵌合抗原受体(CAR)修饰的T细胞疗法近年来发展迅速,最终彻底改变了免疫治疗策略,并提供了显著的抗肿瘤效力,主要用于治疗血液系统肿瘤。然而,移植物抗宿主病(GVHD)以及其他不良反应,如细胞因子释放综合征(CRS)和与CAR-T 细胞输注相关的神经毒性,引发了人们对这种疗法广泛应用的担忧。自然杀伤(NK)细胞因其独特特征,如不受人类白细胞抗原(HLA)配型限制、安全性更优以及与CAR-T 细胞相比具有更好的抗肿瘤活性,已被认为是基于CAR的有前景的替代平台。CAR-NK疗法中缺乏CRS、神经毒性或GVHD,此外还可以使用同种异体NK细胞作为CAR平台进行“现货型”治疗,这开辟了新的战略机遇窗口。本综述强调了CAR构建体近期设计成就,并总结了关于CAR-NK疗法安全性和抗肿瘤效力的临床前研究结果。此外,简要描述了CAR-NK技术的新方法,并列出了目前注册的临床试验。
Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly in treating hematological neoplasms.
However, graft-versus-host disease (GVHD) and other adverse effects, such as cytokine release syndromes (CRS) and neurotoxicity associated with CAR-T cell infusion, have raised some concerns about the broad application of this therapy. Natural killer (NK) cells have been identified as promising alternative platforms for CAR-based therapies because of their unique features, such as a lack of human leukocyte antigen (HLA)-matching restriction, superior safety, and better anti-tumor activity when compared with CAR-T cells.
The lack of CRS, neurotoxicity, or GVHD, in the case of CAR-NK therapy, in addition to the possibility of using allogeneic NK cells as a CAR platform for "off-the-shelf" therapy, opens new windows for strategic opportunities. This review underlines recent design achievements in CAR constructs and summarizes preclinical studies' results regarding CAR-NK therapies' safety and anti-tumor potency.
Additionally, new approaches in CAR-NK technology are briefly described, and currently registered clinical trials are listed.
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