Department of Hematology and Hematopoietic Cell Transplantation.
Hematologic Malignancies Research Institute.
Curr Opin Oncol. 2023 Sep 1;35(5):446-452. doi: 10.1097/CCO.0000000000000968. Epub 2023 Jul 10.
Natural killer (NK) cells are innate lymphoid cells characterized by their ability to attack aberrant and cancerous cells. In contrast to the activation of T-cells, NK cell activation is controlled by the interaction of NK cell receptors and their target cells in a manner independent of antigen organization. Due to NK cells' broad array of activation cues, they have gained great attention as a potential therapeutic agent in cancer immunotherapy.
Ex vivo activation, expansion, and genetic modifications, such as the addition of a chimeric antigen receptor (CAR), will allow the next generation of NK cells to enhance cytotoxicity, promote survival, and create "off-the-shelf" products. In addition to these that are poised to greatly enhance their clinical activity, the inherent lack of potential for causing graft-versus-host disease (GVHD) and cytokine release syndrome (CRS) suggest that CAR NK cells have the potential to be complementary to CAR-T cells as a component of therapeutic strategies for cancer.
In this review, we will provide a general understanding of NK cell biology, CAR-NK cell advantages over CAR-T cell therapy, barriers to making NK cell immunotherapy viable, and current NK cell clinical trials for hematological malignancies and solid tumors. The next generation of NK cells has potential to change the circumstances guiding present cancer immunotherapies.
自然杀伤 (NK) 细胞是先天淋巴细胞,其特征是能够攻击异常和癌变细胞。与 T 细胞的激活不同,NK 细胞的激活受 NK 细胞受体与其靶细胞相互作用的控制,而不受抗原结构的影响。由于 NK 细胞具有广泛的激活信号,它们作为癌症免疫治疗的潜在治疗剂引起了极大的关注。
体外激活、扩增和遗传修饰,如添加嵌合抗原受体 (CAR),将使下一代 NK 细胞能够增强细胞毒性、促进存活并产生“现成”产品。除了这些有望大大提高其临床活性的方法外,固有缺乏引起移植物抗宿主病 (GVHD) 和细胞因子释放综合征 (CRS) 的潜力表明,CAR-NK 细胞有可能与 CAR-T 细胞互补,作为癌症治疗策略的一部分。
在这篇综述中,我们将提供对 NK 细胞生物学的一般理解、CAR-NK 细胞相对于 CAR-T 细胞治疗的优势、使 NK 细胞免疫疗法可行的障碍,以及当前用于血液恶性肿瘤和实体瘤的 NK 细胞临床试验。下一代 NK 细胞有可能改变指导当前癌症免疫疗法的环境。