Interactions between the crystallizable fragment (Fc) domain of antibodies and a plethora of cellular Fc receptors (FcRs) or soluble proteins form a critical link between humoral and innate immunity. In particular, the immunoglobulin G Fc domain is critical for the clearance of target cells by processes that include ( a) cytotoxicity, phagocytosis, or complement lysis; ( b) modulation of inflammation; ( c) antigen presentation; ( d) antibody-mediated receptor clustering; and ( e) cytokine release. More than 30 Fc-engineered antibodies aimed primarily at tailoring these effects for optimal therapeutic outcomes are in clinical evaluation or have already been approved. Nonetheless, our understanding of how FcR engagement impacts various immune cell phenotypes is still largely incomplete. Recent insights into FcR biology coupled with advances in Fc:FcR structural analysis, Fc engineering, and mouse models that recapitulate human biology are helping to fill in existing knowledge gaps. These advances will provide a blueprint on how to fine-tune the Fc domain to achieve optimal therapeutic efficacy.

中文翻译：

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通过操纵 Fc 结构域改善抗体治疗：免疫学和结构方面的考虑

抗体的可结晶片段 (Fc) 结构域与大量细胞 Fc 受体 (FcR) 或可溶性蛋白质之间的相互作用形成体液免疫和先天免疫之间的关键联系。具体而言，免疫球蛋白 G Fc 结构域对于通过以下过程清除靶细胞至关重要，这些过程包括：(a) 细胞毒性、吞噬作用或补体裂解； (b) 调节炎症； (c) 抗原呈递； (d) 抗体介导的受体聚集； (e)细胞因子释放。超过 30 种 Fc 工程抗体主要旨在调整​​这些效应以获得最佳治疗结果，目前正在临床评估中或已经获得批准。尽管如此，我们对 FcR 参与如何影响各种免疫细胞表型的理解仍然很大程度上不完整。最近对 FcR 生物学的见解，加上 Fc:FcR 结构分析、Fc 工程和概括人类生物学的小鼠模型方面的进展，正在帮助填补现有的知识空白。这些进展将为如何微调 Fc 结构域以实现最佳治疗效果提供蓝图。