Zanjan University of Medical Sciences, Zanjan, Iran.
School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Stem Cell Rev Rep. 2021 Dec;17(6):2081-2106. doi: 10.1007/s12015-021-10246-3. Epub 2021 Sep 2.
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.
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方面发挥着关键作用。嵌合抗原受体 (CAR) 的过继细胞疗法 (ACT) 将免疫细胞的特异性重新定向到靶特异性抗原。ACT 最近为癌症治疗创造了一个极好的机会。与 CAR 武装 T 细胞不同，CAR 受体构建物存在一些缺点，例如 MHC 非依赖性、寿命较短、有可能产生现成的免疫产品以及 NK 细胞具有强大的抗肿瘤特性，因此 NK 细胞已成为表达 CAR 的有潜力的替代靶标。在这里，我们旨在提供关于 CAR NK 设计和免疫生物学的最新进展的概述，并描述 CAR 修饰的 NK 细胞作为替代“现成”CAR 载体的潜力。我们还提供了在 CAR NK 细胞生产过程中 NK 细胞的来源列表、将 CAR 遗传序列转导到 NK 细胞的不同方法、CAR T 和 CAR NK 之间的区别，以及当前研究中 CAR NK 靶向的肿瘤抗原。此外，我们还提供了 CAR NK 治疗的最近发表的临床前和临床研究数据，并列出了已完成和正在进行的临床试验。为了实现具有更高疗效和安全性的 CAR NK 产品，我们讨论了 CAR NK 细胞转导和扩增的当前挑战、CAR NK 治疗的副作用以及限制 CAR NK 细胞最佳疗效的挑战，并建议了可能的解决方案，以增强 CAR NK 细胞的持久性、功能、安全性和疗效，特别关注实体瘤。
