Zhang Yalan, Zhou Weilin, Yang Jiangping, Yang Jinrong, Wang Wei
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, 610041, People's Republic of China.
Department of Head and Neck Oncology and Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
Exp Hematol Oncol. 2023 Aug 10;12(1):70. doi: 10.1186/s40164-023-00431-0.
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.
自然杀伤（NK）细胞是固有免疫系统的独特组成部分，是应激细胞和转化细胞的固有杀手。基于其杀伤癌细胞的强大能力以及对健康细胞的良好耐受性，NK细胞已成功应用于过继性细胞疗法来治疗癌症患者。近年来，嵌合抗原受体（CAR）-T细胞的临床成功证明了基因操纵的免疫细胞作为抗癌主力军的巨大潜力。借鉴成熟的基因转移技术和CAR-T疗法的先进策略，NK细胞已被迅速探索为基于CAR疗法的有前景候选者。越来越多的研究使用多种来源的CAR-NK细胞来靶向多种癌症相关抗原，显示出显著的效果和令人鼓舞的安全性。CAR-NK细胞的临床试验也显示出其在治疗血液肿瘤方面令人印象深刻的治疗效果，但用于实体瘤的CAR-NK细胞疗法仍处于初始阶段。在本综述中，我们展示了NK细胞作为基于CAR工程的潜在平台的优势，然后总结了最新临床前和临床研究中CAR-NK疗法的结果和策略。最后，我们评估了CAR-NK疗法中仍然存在的挑战，并描述了可帮助我们设计未来前瞻性解决方案的现有策略。
