Center for Virology and Vaccine Research (CVVR), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge, Massachusetts, USA.
J Leukoc Biol. 2019 Jun;105(6):1253-1259. doi: 10.1002/JLB.MR0718-303R. Epub 2019 Feb 7.
NK cells play a critical role in antiviral and antitumor responses. Although current NK cell immune therapies have focused primarily on cancer biology, many of these advances can be readily applied to target HIV/simian immunodeficiency virus (SIV)-infected cells. Promising developments include recent reports that CAR NK cells are capable of targeted responses while producing less off-target and toxic side effects than are associated with CAR T cell therapies. Further, CAR NK cells derived from inducible pluripotent stem cells or cell lines may allow for more rapid "off-the-shelf" access. Other work investigating the IL-15 superagonist ALT-803 (now N803) may also provide a recourse for enhancing NK cell responses in the context of the immunosuppressive and inflammatory environment of chronic HIV/SIV infections, leading to enhanced control of viremia. With a broader acceptance of research supporting adaptive functions in NK cells it is likely that novel immunotherapeutics and vaccine modalities will aim to generate virus-specific memory NK cells. In doing so, better targeted NK cell responses against virus-infected cells may usher in a new era of NK cell-tuned immune therapy.
自然杀伤 (NK) 细胞在抗病毒和抗肿瘤反应中发挥着关键作用。虽然当前的 NK 细胞免疫疗法主要集中在癌症生物学上，但这些进展中的许多都可以很容易地应用于靶向 HIV/猿猴免疫缺陷病毒 (SIV) 感染的细胞。有希望的发展包括最近的报道，CAR NK 细胞能够进行靶向反应，而产生的脱靶和毒性副作用比 CAR T 细胞疗法要少。此外，来自诱导多能干细胞或细胞系的 CAR NK 细胞可能允许更快地“现成”获得。其他研究白细胞介素 15 超激动剂 ALT-803（现为 N803）的工作也可能为增强 NK 细胞在慢性 HIV/SIV 感染的免疫抑制和炎症环境中的反应提供一种手段，从而增强对病毒血症的控制。随着对 NK 细胞适应性功能的研究得到更广泛的认可，新型免疫疗法和疫苗模式可能旨在产生针对病毒的记忆性 NK 细胞。这样，针对病毒感染细胞的更有针对性的 NK 细胞反应可能开创 NK 细胞免疫治疗的新时代。
