Division of Antibody-Based Immunotherapy, Department of Internal Medicine II, Christian Albrechts University and University Hospital Schleswig-Holstein, Kiel, Germany.
Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, University Hospital, LMU Munich, Munich, Germany.
Clin Exp Immunol. 2022 Jul 22;209(1):22-32. doi: 10.1093/cei/uxac028.
Natural killer (NK) cells exert an important role in cancer immune surveillance. Recognition of malignant cells and controlled activation of effector functions are facilitated by the expression of activating and inhibitory receptors, which is a complex interplay that allows NK cells to discriminate malignant cells from healthy tissues. Due to their unique profile of effector functions, the recruitment of NK cells is attractive in cancer treatment and a key function of NK cells in antibody therapy is widely appreciated. In recent years, besides the low-affinity fragment crystallizable receptor for immunoglobulin G (FcγRIIIA), the activating natural killer receptors p30 (NKp30) and p46 (NKp46), as well as natural killer group 2 member D (NKG2D), have gained increasing attention as potential targets for bispecific antibody-derivatives to redirect NK cell cytotoxicity against tumors. Beyond modulation of the receptor activity on NK cells, therapeutic targeting of the respective ligands represents an attractive approach. Here, novel therapeutic approaches to unleash NK cells by engagement of activating NK-cell receptors and alternative strategies targeting their tumor-expressed ligands in cancer therapy are summarized.
自然杀伤 (NK) 细胞在癌症免疫监测中发挥着重要作用。通过表达激活和抑制受体，促进了对恶性细胞的识别和效应功能的受控激活，这是一种复杂的相互作用，使 NK 细胞能够将恶性细胞与健康组织区分开来。由于其独特的效应功能特征，NK 细胞的募集在癌症治疗中具有吸引力，并且 NK 细胞在抗体治疗中的关键功能已得到广泛认可。近年来，除了免疫球蛋白 G 的低亲和力片段结晶区受体 (FcγRIIIA) 外，激活的自然杀伤受体 p30 (NKp30) 和 p46 (NKp46) 以及自然杀伤组 2 成员 D (NKG2D) 作为双特异性抗体衍生物的潜在靶点，以重新定向 NK 细胞对肿瘤的细胞毒性作用，引起了越来越多的关注。除了调节 NK 细胞上的受体活性外，针对各自配体的治疗性靶向也是一种有吸引力的方法。在这里，总结了通过激活 NK 细胞受体的结合来释放 NK 细胞的新型治疗方法，以及在癌症治疗中靶向其肿瘤表达配体的替代策略。
