Natural killer cells and immunotherapy based on monoclonal antibodies

Magdalena Pencheva-Demireva, K. Kavaldzhieva, Nikola J. Mladenov, T. Markova, D. Dimitrova-Dikanarova
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Abstract

Natural killer (NK) cells are effector lymphocytes of innate immunity needed to protect against stressed cells and to destroy tumor cells and virus-infected cells. These cells play an important role in the immune surveillance of malignant cells, preventing their uncontrolled growth. Natural killer cells recognize target cells directly through their receptors, which bind to various determinants on the surface of the target cell. The receptor-ligand (secretory or membrane-bound) interaction between the NK cells and the target cells determines NK’s cell activity. The use of monoclonal antibodies in tumor therapy has increased significantly in the recent years. These antibodies are intended to block inhibitory receptors (immune checkpoint inhibitors) expressed by immune cells or to block their ligands expressed by tumor cells. Examples of such immune checkpoint molecules are the following receptors: cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and others. This blocking inhibits tumor growth by enabling immune system reactivation. The advances in cellular immunobiology that have provided the establishment of blocking monoclonal antibodies (ipilimumab, nivolumab, etc.) and increased NK cell proliferative activity are promising therapies for neoplasms. Biomed Rev 2020; 31: 61-65
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自然杀伤细胞和基于单克隆抗体的免疫治疗
自然杀伤细胞(NK细胞)是先天免疫的效应淋巴细胞,需要保护免受应激细胞和破坏肿瘤细胞和病毒感染的细胞。这些细胞在恶性细胞的免疫监视中发挥重要作用,防止其不受控制的生长。自然杀伤细胞通过与靶细胞表面的各种决定因子结合的受体直接识别靶细胞。NK细胞与靶细胞之间的受体-配体(分泌性或膜结合性)相互作用决定了NK细胞的活性。近年来,单克隆抗体在肿瘤治疗中的应用显著增加。这些抗体旨在阻断免疫细胞表达的抑制性受体(免疫检查点抑制剂)或阻断肿瘤细胞表达的其配体。这种免疫检查点分子的例子有以下受体:细胞毒性T淋巴细胞相关蛋白4 (CTLA-4)、程序性细胞死亡蛋白1 (PD-1)等。这种阻断通过使免疫系统重新激活来抑制肿瘤生长。细胞免疫生物学的进步提供了阻断单克隆抗体(ipilimumab, nivolumab等)的建立和NK细胞增殖活性的增加,是治疗肿瘤的有希望的治疗方法。Biomed Rev 2020;31日:61 - 65
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