嵌合抗原受体自然杀伤细胞疗法研究进展及展望

Research progress and prospect of chimeric antigen receptor natural killer cell immunotherapy

自然杀伤(NK)细胞是先天免疫系统的主要组成部分。基于其对肿瘤细胞的有效杀伤能力和对健康细胞的良好耐受性,NK细胞已成功地用于过继细胞疗法以治疗肿瘤患者。近年来,嵌合抗原受体(CAR)-T细胞的临床成功,证明了基因修饰的免疫细胞在抗肿瘤领域的巨大潜力。NK细胞凭借优越的低免疫原性也迅速成为基于CAR修饰疗法的新型免疫工具细胞。目前已经开展的多项临床试验中,多种来源的CAR-NK细胞均展现出较为优越的治疗效果和安全性,但靶向实体瘤CAR-NK细胞治疗仍处于初始阶段。本文系统梳理了CAR-NK细胞在临床上取得阶段性进展,同时也指出CAR-NK细胞疗法的局限性,旨在为进一步优化和升级CAR-NK细胞疗法提供参考。

Natural killer(NK)cells constitute the principal components of the innate immune system.Due to their potent cytotoxicity against tumor cells and favorable tolerance towards healthy cells,NK cells have been effectively employed in adoptive cell therapy for cancer patients.In recent years,the remarkable clinical success of chimeric antigen receptor(CAR)-T cells has demonstrated the immense potential of genetically modified immune cells in anti-tumor applications.Owing to their inherent low immunogenicity,NK cells have rapidly emerged as a novel class of CAR-modified therapeutic immune tools.Several ongoing clinical trials have exhibited superior therapeutic efficacy and safety profiles of CAR-NK cells derived from diverse sources.However,targeting solid tumors with CAR-NK cell therapy is still at an early stage.This review comprehensively summarizes the clinical advancements achieved by CAR-NK cell therapy while highlighting its limitations,aiming to provide insights for further optimization and advancement.