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:Chimeric antigen receptor engineered natural killer cells for cancer therapy.
Chimeric antigen receptor engineered natural killer cells for cancer therapy.
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自然杀伤(NK)细胞是固有免疫系统中一个独特的组成部分,是应激细胞和转化细胞的天然杀手。基于其强大的杀伤癌细胞能力和对健康细胞的良好耐受性,NK细胞已被成功应用于过继细胞疗法中以治疗癌症患者。近年来,嵌合抗原受体(CAR)-T细胞的临床成功已证明基因改造免疫细胞作为抗癌主力军的巨大潜力。借鉴成熟基因转移技术和CAR-T 疗法先进策略的经验教训,NK细胞作为CAR基础疗法的有前景候选者已被迅速探索。越来越多的研究利用多种来源的CAR-NK细胞靶向广泛的癌症相关抗原,显示出显著的结果和令人鼓舞的安全性特征。CAR-NK细胞的临床试验也显示了其在治疗血液肿瘤方面令人印象深刻的治疗疗效,但CAR-NK细胞疗法用于实体瘤仍处于初始阶段。在本综述中,我们介绍了NK细胞作为CAR基础工程潜在平台的优势特征,然后总结了CAR-NK疗法在最新临床前和临床研究中的结果和策略。
最后,我们评估了CAR-NK疗法中仍存在的挑战,并描述了可帮助我们制定未来前瞻性解决方案的现有策略。
Natural killer (NK) cells, a unique component of the innate immune system, are inherent killers of stressed and transformed cells. Based on their potent capacity to kill cancer cells and good tolerance of healthy cells, NK cells have been successfully employed in adoptive cell therapy to treat cancer patients. In recent years, the clinical success of chimeric antigen receptor (CAR)-T cells has proven the vast potential of gene-manipulated immune cells as the main force to fight cancer. Following the lessons learned from mature gene-transfer technologies and advanced strategies in CAR-T therapy, NK cells have been rapidly explored as a promising candidate for CAR-based therapy.
An exponentially growing number of studies have employed multiple sources of CAR-NK cells to target a wide range of cancer-related antigens, showing remarkable outcomes and encouraging safety profiles. Clinical trials of CAR-NK cells have also shown their impressive therapeutic efficacy in the treatment of hematological tumors, but CAR-NK cell therapy for solid tumors is still in the initial stages.
In this review, we present the favorable profile of NK cells as a potential platform for CAR-based engineering and then summarize the outcomes and strategies of CAR-NK therapies in up-to-date preclinical and clinical investigations.
Finally, we evaluate the challenges remaining in CAR-NK therapy and describe existing strategies that can assist us in devising future prospective solutions.
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