Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences and Medical Center, University Of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs Anhui, University of Science and Technology of China, Hefei, Anhui 230027, China.
Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences and Medical Center, University Of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs Anhui, University of Science and Technology of China, Hefei, Anhui 230027, China.
Semin Immunol. 2017 Jun;31:37-54. doi: 10.1016/j.smim.2017.07.009. Epub 2017 Aug 31.
Natural killer (NK) cells can induce an antigen-independent immune response against malignant cells. A growing number of scientific reports and clinical studies have shown promising anti-tumor effects when using NK cell-based immunotherapy. Currently, various approaches are being used to enhance the number and function of NK cells. One approach uses cytokines to selectively boost both the number as well as the efficacy of anti-tumor functions of NK cells. Another emerging approach focuses on checkpoint inhibitors targeting the NK cell receptor. Furthermore, bi-specific and tri-specific engagers have been developed to enhance the specific immune response by cross-linking specific tumor antigens to effector cells. In addition, NK cell adoptive transfer therapies have shown promising prospects. Among the various sources of adoptive transfer NK cells, allogeneic haploidentical NK cells that have undergone short- or long-term activation or expansion have also demonstrated effective anti-tumor effects with a low rate of rejection and side effects. CAR-NKs, derived from a new type of genetic modification, show enhanced NK cell cytotoxicity, specificity, and targeting. These NK cell-based therapies have exhibited promising results in clinical trials with malignant tumors. In this review, the current progress on NK cell-based therapeutic approaches, NK cell manufacturing techniques and tumor therapy outcomes are discussed.
自然杀伤 (NK) 细胞可以诱导针对恶性细胞的非抗原依赖性免疫反应。越来越多的科学报告和临床研究表明,使用基于 NK 细胞的免疫疗法具有有前途的抗肿瘤作用。目前,正在使用各种方法来增加 NK 细胞的数量和功能。一种方法是使用细胞因子选择性地增强 NK 细胞的数量和抗肿瘤功能的功效。另一种新兴的方法侧重于针对 NK 细胞受体的检查点抑制剂。此外,已经开发出双特异性和三特异性衔接子,通过将特异性肿瘤抗原交联到效应细胞上来增强特异性免疫反应。此外,NK 细胞过继转移疗法显示出有希望的前景。在过继转移 NK 细胞的各种来源中,经过短期或长期激活或扩增的同种异体单倍体 NK 细胞也表现出有效的抗肿瘤作用,排斥反应和副作用发生率低。源自新型基因修饰的 CAR-NK 细胞显示出增强的 NK 细胞细胞毒性、特异性和靶向性。这些基于 NK 细胞的疗法在恶性肿瘤的临床试验中显示出有希望的结果。在这篇综述中,讨论了基于 NK 细胞的治疗方法、NK 细胞制造技术和肿瘤治疗结果的最新进展。