Antibodies are the cardinal effector molecules of the immune system and are being leveraged with enormous success as biotherapeutic drugs. A key part of the adaptive immune response is the production of an epitope-diverse, polyclonal antibody mixture that is capable of neutralizing invading pathogens or disease-causing molecules through binding interference and by mediating humoral and cellular effector functions. Avidity — the accumulated binding strength derived from the affinities of multiple individual non-covalent interactions — is fundamental to virtually all aspects of antibody biology, including antibody–antigen binding, clonal selection and effector functions. The manipulation of antibody avidity has since emerged as an important design principle for enhancing or engineering novel properties in antibody biotherapeutics. In this Review, we describe the multiple levels of avidity interactions that trigger the overall efficacy and control of functional responses in both natural antibody biology and their therapeutic applications. Within this framework, we comprehensively review therapeutic antibody mechanisms of action, with particular emphasis on engineered optimizations and platforms. Overall, we describe how affinity and avidity tuning of engineered antibody formats are enabling a new wave of differentiated antibody drugs with tailored properties and novel functions, promising improved treatment options for a wide variety of diseases.

抗体是免疫系统的主要效应分子，并且作为生物治疗药物获得了巨大成功。适应性免疫反应的一个关键部分是产生表位多样化的多克隆抗体混合物，该混合物能够通过结合干扰和介导体液和细胞效应功能来中和入侵的病原体或致病分子。亲和力——源自多个个体非共价相互作用的亲和力的累积结合强度——是抗体生物学几乎所有方面的基础，包括抗体-抗原结合、克隆选择和效应器功能。此后，抗体亲和力的操作已成为增强或工程化抗体生物治疗学新特性的重要设计原则。在这篇评论中，我们描述了在天然抗体生物学及其治疗应用中触发功能反应的整体功效和控制的多层次的亲和力相互作用。在这个框架内，我们全面回顾了治疗性抗体的作用机制，特别强调了工程优化和平台。总体而言，我们描述了工程抗体形式的亲和力和亲和力调整如何促成具有定制特性和新功能的新一波差异化抗体药物，并有望改善各种疾病的治疗选择。我们全面回顾了治疗性抗体的作用机制，特别强调了工程优化和平台。总体而言，我们描述了工程抗体形式的亲和力和亲和力调整如何促成具有定制特性和新功能的新一波差异化抗体药物，并有望改善各种疾病的治疗选择。我们全面回顾了治疗性抗体的作用机制，特别强调了工程优化和平台。总体而言，我们描述了工程抗体形式的亲和力和亲和力调整如何促成具有定制特性和新功能的新一波差异化抗体药物，并有望改善各种疾病的治疗选择。