Harnessing natural killer cells to develop next-generation cellular immunotherapy.
Harnessing natural killer cells to develop next-generation cellular immunotherapy.
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DOI：
10.1002/cdt3.40
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发表时间：
2022-12
影响因子：
--
通讯作者：
Zhou, Yubin
中科院分区：
文献类型：
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作者：
Liu, Siyao;Nguyen, Kaycee;Park, Dongyong;Wong, Nelson;Wang, Anson;Zhou, Yubin
细胞免疫疗法利用人体自身的免疫系统，通过使用工程T细胞，巨噬细胞或自然杀伤（NK）细胞来对抗癌症。与常用于治疗血液恶性肿瘤的嵌合抗原受体T（CAR-T）细胞相比，CAR-NK细胞显示出显著的治疗效果，同时显示出增强的安全性，降低的移植物抗宿主病风险，更少的副作用和增强的抗肿瘤疗效。临床前试验揭示了过继性CAR-NK细胞疗法在动物模型中减少甚至消除血液恶性肿瘤和实体瘤的巨大潜力。本文介绍了CAR-NK细胞的设计原理，重点介绍了CAR-NK细胞临床前测试和临床试验的最新进展，简要探讨了CAR-NK治疗的主要障碍，并讨论了克服这些挑战的潜在解决方案。鉴于免疫细胞工程的基础和转化研究的加速进展，CAR-NK细胞疗法有望成为下一代基于细胞的免疫疗法的重要竞争者和重要补充。CAR-NK细胞疗法作为一种有前途的免疫选择，通过克服耐药肿瘤微环境来减少血液肿瘤和实体瘤。CAR-NK细胞疗法具有上级安全性，对肿瘤细胞具有有效的细胞毒性，使其成为癌症治疗第四支柱的新成员。在这篇综述中，我们重点介绍了基于CAR-NK细胞的免疫治疗的最新进展。我们还讨论了CAR-NK细胞疗法临床转化面临的主要障碍，并提出了克服这些挑战的潜在策略。
Cellular immunotherapy harnesses the body's own immune system to fight cancer by using engineered T cells, macrophages, or natural killer (NK) cells. Compared to chimeric antigen receptor T (CAR‐T) cells that are commonly used to treat hematological malignancies, CAR‐NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety, reduced risk of graft‐versus‐host disease, fewer side effects, and amplified antitumor efficacy. Preclinical trials have unveiled the high potential of adoptive CAR‐NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models. We brought forth herein the design principle of CAR‐NK cells, highlighted the latest progress in the preclinical testing and clinical trials of CAR‐NK cells, briefly delved into discussed major roadblocks in CAR‐NK therapy, and discussed potential solutions to surmount these challenges. Given the accelerated progress in both basic and translational studies on immune cell engineering, CAR‐NK cell therapy promises to become a serious contender and important addition to the next‐generation cell‐based immunotherapy. CAR‐NK cell therapy emerges as a promising immunotherapeutic option to curtail both hematological neoplasms and solid tumors by overcoming the resistant tumor microenvironment. CAR‐NK cell therapy exhibits a superior safety profile with effective cytotoxicity against tumor cells, making it a new addition to the fourth pillar of cancer therapy. In this review, we highlight the latest progress in the CAR‐NK cell‐based immunotherapy. We also discuss major roadblocks facing the clinical translation of CAR‐NK cell therapy, and present potential strategies to surmount these challenges.