Zhang Leisheng, Meng Yuan, Feng Xiaoming, Han Zhongchao
Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province & NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, 730000, China.
Center for Cellular Therapies, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, 250014, China.
Biomark Res. 2022 Mar 18;10(1):12. doi: 10.1186/s40364-022-00364-6.
Natural killer (NK) cells are unique innate immune cells and manifest rapid and potent cytotoxicity for cancer immunotherapy and pathogen removal without the requirement of prior sensitization or recognition of peptide antigens. Distinguish from the T lymphocyte-based cythotherapy with toxic side effects, chimeric antigen receptor-transduced NK (CAR-NK) cells are adequate to simultaneously improve efficacy and control adverse effects including acute cytokine release syndrome (CRS), neurotoxicity and graft-versus-host disease (GVHD). Moreover, considering the inherent properties of NK cells, the CAR-NK cells are "off-the-shelf" product satisfying the clinical demand for large-scale manufacture for cancer immunotherapy attribute to the cytotoxic effect via both NK cell receptor-dependent and CAR-dependent signaling cascades. In this review, we mainly focus on the latest updates of CAR-NK cell-based tactics, together with the opportunities and challenges for cancer immunotherapies, which represent the paradigm for boosting the immune system to enhance antitumor responses and ultimately eliminate malignancies. Collectively, we summarize and highlight the auspicious improvement in CAR-NK cells and will benefit the large-scale preclinical and clinical investigations in adoptive immunotherapy.
自然杀伤（NK）细胞是独特的固有免疫细胞，在癌症免疫治疗和病原体清除中表现出快速而强大的细胞毒性，无需预先致敏或识别肽抗原。与具有毒性副作用的基于T淋巴细胞的细胞疗法不同，嵌合抗原受体转导的NK（CAR-NK）细胞足以同时提高疗效并控制包括急性细胞因子释放综合征（CRS）、神经毒性和移植物抗宿主病（GVHD）在内的不良反应。此外，考虑到NK细胞的固有特性，CAR-NK细胞是一种“现货”产品，由于其通过NK细胞受体依赖性和CAR依赖性信号级联产生细胞毒性作用，满足了癌症免疫治疗大规模生产的临床需求。在本综述中，我们主要关注基于CAR-NK细胞策略的最新进展，以及癌症免疫治疗面临的机遇和挑战，这些代表了增强免疫系统以增强抗肿瘤反应并最终消除恶性肿瘤的范例。总的来说，我们总结并强调了CAR-NK细胞的良好进展，这将有利于过继性免疫治疗的大规模临床前和临床研究。
