The clinical application of monoclonal antibodies (mAbs) has revolutionized the field of cancer therapy, as it has enabled the successful treatment of previously untreatable types of cancer. Different mechanisms play a role in the anti‐tumour effect of mAbs. These include blocking of tumour‐specific growth factor receptors or of immune modulatory molecules as well as complement and cell‐mediated tumour cell lysis. Thus, for many mAbs, Fc‐mediated effector functions critically contribute to the efficacy of treatment. As immunoglobulin (Ig) isotypes differ in their ability to bind to Fc receptors on immune cells as well as in their ability to activate complement, they differ in the immune responses they activate. Therefore, the choice of antibody isotype for therapeutic mAbs is dictated by its intended mechanism of action. Considering that clinical efficacy of many mAbs is currently achieved only in subsets of patients, optimal isotype selection and Fc optimization during antibody development may represent an important step towards improved patient outcome. Here, we discuss the current knowledge of the therapeutic effector functions of different isotypes and Fc‐engineering strategies to improve mAbs application.

中文翻译：

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基于抗体的癌症治疗的同种型选择

单克隆抗体 (mAb) 的临床应用彻底改变了癌症治疗领域，因为它能够成功治疗以前无法治愈的癌症类型。不同的机制在 mAb 的抗肿瘤作用中发挥作用。这些包括阻断肿瘤特异性生长因子受体或免疫调节分子以及补体和细胞介导的肿瘤细胞裂解。因此，对于许多 mAb，Fc 介导的效应器功能对治疗效果至关重要。由于免疫球蛋白 (Ig) 同种型在与免疫细胞上的 Fc 受体结合的能力以及激活补体的能力方面不同，因此它们激活的免疫反应也不同。因此，治疗性 mAb 的抗体同种型的选择取决于其预期的作用机制。考虑到许多 mAb 的临床疗效目前仅在患者亚群中实现，抗体开发过程中的最佳同种型选择和 Fc 优化可能代表改善患者预后的重要一步。在这里，我们讨论了当前对不同同种型的治疗效应功能的了解以及改进 mAb 应用的 Fc 工程策略。