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自然杀伤细胞和单克隆抗体:成功依赖抗体依赖细胞毒性杀伤肿瘤细胞的两个伙伴。

Natural Killer cells and monoclonal antibodies: Two partners for successful antibody dependent cytotoxicity against tumor cells.

机构信息

Lorraine University, CNRS UMR 7365, Team 6, Campus Santé, Vandoeuvre-les-Nancy, France; CHRU Nancy, Cell Therapy and Tissue Bank Unit, Vandoeuvre-Les-Nancy, France.

Lorraine University, CNRS UMR7039, Team BioSIS, Campus Santé, Vandoeuvre-Les-Nancy, France.

出版信息

Crit Rev Oncol Hematol. 2021 Apr;160:103261. doi: 10.1016/j.critrevonc.2021.103261. Epub 2021 Feb 16.

Abstract

Monoclonal antibodies targeting tumors are one of the most important discoveries in the field of cancer. Although several effective antibodies have been developed, a relapse may occur. One of their mechanisms of action is Antibody Dependent Cell Cytotoxicity (ADCC), by engaging the Fc γ receptor CD16 expressing Natural Killer cells, innate lymphoid cells involved in cancer immunosurveillance and able to kill tumor cells. A lack of NK cells observed in many cancers may therefore be a cause of the low efficacy of antibodies observed in some clinical situations. Here we review clear evidences of the essential partnership between NK cells and antibodies showed in vitro, in vivo, and in clinical trials in different indications, describe the hurdles and ways to enhance ADCC and the evolution of monoclonal antibody therapy. NK cell adoptive immunotherapy combined with monoclonal antibodies may overcome the resistance to the treatment and enhance their efficacy.

摘要

靶向肿瘤的单克隆抗体是癌症领域最重要的发现之一。尽管已经开发出几种有效的抗体,但仍可能会出现复发。其作用机制之一是抗体依赖的细胞细胞毒性(ADCC),通过与表达 Fcγ受体 CD16 的自然杀伤细胞(NK 细胞)结合,NK 细胞是参与癌症免疫监视的固有淋巴细胞,能够杀死肿瘤细胞。因此,在许多癌症中观察到的 NK 细胞缺乏可能是某些临床情况下观察到的抗体疗效低的原因。在这里,我们回顾了体外、体内和不同适应症临床试验中 NK 细胞与抗体之间存在的重要伙伴关系的明确证据,描述了增强 ADCC 的障碍和方法以及单克隆抗体治疗的发展。NK 细胞过继免疫疗法与单克隆抗体联合使用可能会克服对治疗的抵抗并提高其疗效。

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