Natural Killer (NK) cells are critical members of the innate immunity lymphocytes and have a critical role in host defense against malignant cells. Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR) redirects the specificity of the immune cell against a target-specific antigen. ACT has recently created an outstanding opportunity for cancer treatment. Unlike CAR-armored T cells which hadnsome shortcomings as the CAR-receiving construct, Major histocompatibility complex (MHC)-independency, shorter lifespan, the potential to produce an off-the-shelf immune product, and potent anti-tumor properties of the NK cells has introduced NK cells as a potent alternative target for expression of CAR. Here, we aim to provide an updated overview on the current improvements in CAR NK design and immunobiology and describe the potential of CAR-modified NK cells as an alternative “off-the-shelf” carrier of CAR. We also provide lists for the sources of NK cells in the process of CAR NK cell production, different methods for transduction of the CAR genetic sequence to NK cells, the differences between CAR T and CAR NK, and CAR NK-targeted tumor antigens in current studies. Additionally, we provide data on recently published preclinical and clinical studies of CAR NK therapy and a list of finished and ongoing clinical trials. For achieving CAR NK products with higher efficacy and safety, we discuss current challenges in transduction and expansion of CAR NK cells, CAR NK therapy side effects, and challenges that limit the optimal efficacy of CAR NK cells and recommend possible solutions to enhance the persistence, function, safety, and efficacy of CAR NK cells with a special focus on solid tumors.

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中文翻译：

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嵌合抗原受体工程自然杀伤 (CAR NK) 细胞在癌症治疗中的应用；最新进展和未来前景

自然杀伤 (NK) 细胞是先天免疫淋巴细胞的重要成员，在宿主防御恶性细胞中起关键作用。使用嵌合抗原受体 (CAR) 的过继细胞疗法 (ACT) 重定向免疫细胞对靶特异性抗原的特异性。ACT 最近为癌症治疗创造了绝佳的机会。与作为 CAR 受体结构存在一些缺点的 CAR 装甲 T 细胞不同，主要组织相容性复合物 (MHC) 独立性、较短的寿命、产生现成免疫产品的潜力以及 NK 的有效抗肿瘤特性细胞已将 NK 细胞作为 CAR 表达的有效替代靶标。这里，我们旨在提供有关 CAR NK 设计和免疫生物学当前改进的最新概述，并描述 CAR 修饰的 NK 细胞作为 CAR 替代“现成”载体的潜力。我们还提供了 CAR NK 细胞生产过程中 NK 细胞的来源、CAR 基因序列转导 NK 细胞的不同方法、CAR T 和 CAR NK 之间的差异以及目前 CAR NK 靶向肿瘤抗原的清单。学习。此外，我们还提供了最近发表的 CAR NK 疗法的临床前和临床研究数据以及已完成和正在进行的临床试验列表。为了获得具有更高功效和安全性的 CAR NK 产品，我们讨论了当前在 CAR NK 细胞转导和扩增方面的挑战、CAR NK 治疗副作用、

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