Approved for the treatment of autoimmune diseases, hematological malignancies, and solid cancers, several monoclonal antibodies (mAb) make use of complement in their mechanism of action. Such an assessment is based on comprehensive investigations that used mouse models, in vitro studies, and analyses from patients at initiation (basal level to highlight deficiencies) and after treatment initiation (mAb impact on complement), which have further provided key insights into the importance of the complement activation and/or complement deficiencies in mAb activity. Accordingly, new approaches can now be developed with the final objective of increasing the clinical efficacy of mAb. These improvements include (i) the concurrent administration of fresh frozen plasma during mAb therapy; (ii) mAb modifications such as immunoglobulin G subclass switching, Fc mutation, or IgG hexamerization to improve the fixation and activation of C1q; (iii) optimization of the target recognition to induce a higher complement-dependent cytotoxicity (CDC) and/or complement-dependant cellular cytotoxicity (CDCC); and (iv) the control of soluble and cellular complement inhibitors.

中文翻译：

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补体系统：免疫治疗中被忽视的途径。

批准用于治疗自身免疫性疾病，血液恶性肿瘤和实体癌的几种单克隆抗体（mAb）在其作用机制中使用了补体。此类评估基于全面的研究，该研究使用了小鼠模型，体外研究，以及在治疗开始时（基础水平以突出缺陷）和治疗开始后（mAb对补体的影响）对患者进行的分析，从而进一步提供了重要意义的关键见解。 mAb活性中补体激活和/或补体缺陷的发生。因此，现在可以开发新方法，其最终目的是提高mAb的临床功效。这些改进包括（i）在mAb治疗期间同时施用新鲜的冷冻血浆；（ii）mAb修饰，例如免疫球蛋白G亚类转换，Fc突变或IgG六聚化以改善C1q的固定和活化；（iii）优化靶标识别，以诱导更高的补体依赖性细胞毒性（CDC）和/或补体依赖性细胞毒性（CDCC）；（iv）控制可溶性和细胞补体抑制剂。