Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud. Monterrey CP 64710, Mexico.
Curr Gene Ther. 2022;22(4):303-318. doi: 10.2174/1566523222666211217091724.
The Chimeric Antigen Receptor (CAR) has arisen as a powerful synthetic biology-based technology with demonstrated versatility for implementation in T and NK cells. Despite CAR T cell successes in clinical trials, several challenges remain to be addressed regarding adverse events and long-term efficacy. NK cells present an attractive alternative with intrinsic advantages over T cells for treating solid and liquid tumors. Early preclinical and clinical trials suggest at least two major advantages: improved safety and an off-the-shelf application in patients due to its HLA independence. Due to the early stages of CAR NK translation to clinical trials, limited data is currently available. By analyzing these results, it seems that CAR NK cells could offer a reduced probability of Cytokine Release Syndrome (CRS) or Graft versus Host Disease (GvHD) in cancer patients, reducing safety concerns. Furthermore, NK cell therapy approaches may be boosted by combining it with immunological checkpoint inhibitors and by implementing genetic circuits to direct CAR-bearing cell behavior. This review provides a description of the CAR technology for modifying NK cells and the translation from preclinical studies to early clinical trials in this new field of immunotherapy.
嵌合抗原受体 (CAR) 已成为一种强大的基于合成生物学的技术，在 T 细胞和 NK 细胞中的应用具有多种功能。尽管 CAR-T 细胞在临床试验中取得了成功，但在不良事件和长期疗效方面仍存在一些需要解决的挑战。NK 细胞具有内在优势，相对于 T 细胞来说是治疗实体瘤和液体瘤的一种有吸引力的替代方法。早期的临床前和临床试验表明，至少有两个主要优势：由于其 HLA 独立性，提高了安全性和可在患者中进行现成应用。由于 CAR-NK 向临床试验的转化仍处于早期阶段，目前可用的数据有限。通过分析这些结果，似乎 CAR-NK 细胞可以降低癌症患者发生细胞因子释放综合征 (CRS) 或移植物抗宿主病 (GvHD) 的概率，降低安全性担忧。此外，通过与免疫检查点抑制剂联合使用，并实施遗传回路来指导 CAR 载体细胞的行为，NK 细胞疗法可能会得到增强。本文综述了用于修饰 NK 细胞的 CAR 技术，并描述了该技术从临床前研究到免疫治疗新领域早期临床试验的转化。
