CAR-NK细胞治疗血液肿瘤的研究进展

Outlook for CAR-NK immunotherapy in hematological malignancy

NK细胞作为固有免疫细胞在肿瘤免疫监视中发挥重要作用。相比CAR-T其神经毒性、细胞因子释放综合征等不良反应和移植物抗宿主病鲜有发生,因此有希望成为嵌合抗原受体细胞免疫治疗更好的细胞来源。目前CAR-NK细胞的研究仍多使用根据T细胞激活原理设计的CAR。该文针对NK细胞激活原理设计的CAR结构、可用于免疫治疗的NK细胞来源和CAR-NK细胞在白血病、淋巴瘤、骨髓瘤的临床前景及临床研究进展进行综述。分析得出,“现货型”CAR-NK细胞将是血液肿瘤治疗的新方向,如何增加CAR-NK细胞在体内的存活时间仍是其应用于临床亟须解决的问题。

Natural killer cell plays an important role in immune surveillance as a crucial component of the innate system.It’s a promising alternative platform for CAR engineering owning to their lower risk of graft versus host disease and incidence of adverse events such as cytokine release syndrome or neurotoxicity.CAR constructs optimized for T-cell signaling and function still make up the majority of studies exploring CAR NK cells.In this review,it focuses on the details of CAR-NK technology,including the design of efficient CAR constructs and NK cell sources.It also provides an outlook on how these CAR-NK cell therapies treating various hematological malignancies,including leukemia,lymphoma and multiple myeloma.Off-the-shelf cellular therapy is likely to be the next frontier for hematological malignancies.Limitation of in vivo survival time for infused cells is the challenge urgently needs to be overcome.