Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, USA.
Program in Immunology, Stanford University School of Medicine, Palo Alto, California, USA.
J Immunother Cancer. 2022 May;10(5). doi: 10.1136/jitc-2022-004693.
Adoptive cell therapy is a rapidly advancing approach to cancer immunotherapy that seeks to facilitate antitumor responses by introducing potent effector cells into the tumor microenvironment. Expanded autologous T cells, particularly T cells with engineered T cell receptors (TCR) and chimeric antigen receptor-T cells have had success in various hematologic malignancies but have faced challenges when applied to solid tumors. As a result, other immune subpopulations may provide valuable and orthogonal options for treatment. Natural killer (NK) cells offer the possibility of significant tumor clearance and recruitment of additional immune subpopulations without the need for prior antigen presentation like in T or B cells that could require removal of endogenous antigen specificity mediated via the T cell receptor (TCR and/or the B ecll receptor (BCR). In recent years, NK cells have been demonstrated to be increasingly important players in the immune response against cancer. Here, we review multiple avenues for allogeneic NK cell therapy, including derivation of NK cells from peripheral blood or umbilical cord blood, the NK-92 immortalized cell line, and induced pluripotent stem cells (iPSCs). We also describe the potential of engineering iPSC-derived NK cells and the utility of this platform. Finally, we consider the benefits and drawbacks of each approach and discuss recent developments in the manufacturing and genetic or metabolic engineering of NK cells to have robust and prolonged antitumor responses in preclinical and clinical settings.
过继细胞疗法是一种癌症免疫疗法的快速发展方法，旨在通过将有效的效应细胞引入肿瘤微环境中来促进抗肿瘤反应。扩增的自体 T 细胞，特别是具有工程化 T 细胞受体 (TCR) 和嵌合抗原受体-T 细胞的 T 细胞，在各种血液恶性肿瘤中取得了成功，但在应用于实体瘤时面临挑战。因此，其他免疫亚群可能为治疗提供有价值的和正交的选择。自然杀伤 (NK) 细胞提供了清除肿瘤和招募额外免疫亚群的可能性，而不需要像 T 或 B 细胞那样进行抗原呈递，T 或 B 细胞可能需要通过 T 细胞受体 (TCR) 和/或 B 细胞受体 (BCR) 来消除内源性抗原特异性。近年来，NK 细胞已被证明是抗肿瘤免疫反应中越来越重要的参与者。在这里，我们综述了多种同种异体 NK 细胞治疗的途径，包括从外周血或脐带血中衍生 NK 细胞、NK-92 永生化细胞系和诱导多能干细胞 (iPSC)。我们还描述了工程化 iPSC 衍生 NK 细胞的潜力和该平台的实用性。最后，我们考虑了每种方法的优缺点，并讨论了 NK 细胞在制造和遗传或代谢工程方面的最新进展，以在临床前和临床环境中产生强大和持久的抗肿瘤反应。
