Department of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Stem Cell Res Ther. 2021 Mar 22;12(1):200. doi: 10.1186/s13287-021-02251-7.
In recent decades, a new method of cellular immunotherapy was introduced based on engineering and empowering the immune effector cells. In this type of immunotherapy, the immune effector cells are equipped with chimeric antigen receptor (CAR) to specifically target cancer cells. In much of the trials and experiments, CAR-modified T cell immunotherapy has achieved very promising therapeutic results in the treatment of some types of cancers and infectious diseases. However, there are also some considerable drawbacks in the clinical application of CAR-T cells although much effort is in progress to rectify the issues. In some conditions, CAR-T cells initiate over-activated and strong immune responses, therefore, causing unexpected side-effects such as systemic cytokine toxicity (i.e., cytokine release syndrome), neurotoxicity, on-target, off-tumor toxicity, and graft-versus-host disease (GvHD). To overcome these limitations in CAR-T cell immunotherapy, NK cells as an alternative source of immune effector cells have been utilized for CAR-engineering. Natural killer cells are key players of the innate immune system that can destroy virus-infected cells, tumor cells, or other aberrant cells with their efficient recognizing capability. Compared to T cells, CAR-transduced NK cells (CAR-NK) have several advantages, such as safety in clinical use, non-MHC-restricted recognition of tumor cells, and renewable and easy cell sources for their preparation. In this review, we will discuss the recent preclinical and clinical studies, different sources of NK cells, transduction methods, possible limitations and challenges, and clinical considerations.
近几十年来，一种新的细胞免疫疗法基于工程和增强免疫效应细胞的方法被引入。在这种免疫疗法中，免疫效应细胞被装备嵌合抗原受体（CAR），以特异性地靶向癌细胞。在许多试验和实验中，CAR 修饰的 T 细胞免疫疗法在治疗某些类型的癌症和传染病方面取得了非常有前景的治疗效果。然而，CAR-T 细胞在临床应用中也存在一些相当大的缺陷，尽管正在进行大量努力来纠正这些问题。在某些情况下，CAR-T 细胞会引发过度激活和强烈的免疫反应，从而导致意想不到的副作用，如全身细胞因子毒性（即细胞因子释放综合征）、神经毒性、靶向、脱靶毒性和移植物抗宿主病（GvHD）。为了克服 CAR-T 细胞免疫疗法的这些局限性，NK 细胞作为免疫效应细胞的替代来源已被用于 CAR 工程。自然杀伤细胞是先天免疫系统的关键参与者，能够通过其有效的识别能力破坏病毒感染的细胞、肿瘤细胞或其他异常细胞。与 T 细胞相比，CAR 转导的 NK 细胞（CAR-NK）具有几个优势，例如在临床使用中的安全性、对肿瘤细胞的非 MHC 限制识别以及可再生和易于制备的细胞来源。在这篇综述中，我们将讨论最近的临床前和临床研究、NK 细胞的不同来源、转导方法、可能的局限性和挑战以及临床考虑。
