Monoclonal antibodies (mAbs) are one of the most widely used drug platforms for infectious diseases or cancer therapeutics because they selectively target pathogens, infectious cells, cancerous cells, and even immune cells. In this way, they mediate the elimination of target molecules and cells with fewer side effects than other therapeutic modalities. In particular, cancer therapeutic mAbs can recognize cell-surface proteins on target cells and then kill the targeted cells by multiple mechanisms that are dependent upon a fragment crystallizable (Fc) domain interacting with effector Fc gamma receptors, including antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated phagocytosis. Extensive engineering efforts have been made toward tuning Fc functions by either reinforcing (e.g. for targeted therapy) or disabling (e.g. for immune checkpoint blockade therapy) effector functions and prolonging the serum half-lives of antibodies, as necessary. In this report, we review Fc engineering efforts to improve therapeutic potency, and propose future antibody engineering directions that can fulfill unmet medical needs.

单克隆抗体 (mAb) 是传染病或癌症治疗中使用最广泛的药物平台之一，因为它们选择性地靶向病原体、感染细胞、癌细胞甚至免疫细胞。通过这种方式，与其他治疗方式相比，它们能够以更少的副作用介导目标分子和细胞的消除。特别是，癌症治疗 mAb 可以识别靶细胞上的细胞表面蛋白，然后通过多种机制杀死靶细胞，这些机制依赖于与效应 Fc γ 受体相互作用的可结晶片段 (Fc) 结构域，包括抗体依赖性细胞介导的细胞毒性和抗体依赖性细胞介导的吞噬作用。通过增强（例如用于靶向治疗）或禁用（例如 用于免疫检查点阻断治疗）效应器功能并根据需要延长抗体的血清半衰期。在本报告中，我们回顾了 Fc 工程为提高治疗效力所做的努力，并提出了未来可以满足未满足的医疗需求的抗体工程方向。