Sanofi, Cambridge, MA, USA.
Former Sanofi Employee Affiliated with Sanofi at Time of Study.
Clin Immunol. 2023 Jun;251:109629. doi: 10.1016/j.clim.2023.109629. Epub 2023 May 4.
The objective of this study was to characterize the complement-inhibiting activity of SAR445088, a novel monoclonal antibody specific for the active form of C1s. Wieslab® and hemolytic assays were used to demonstrate that SAR445088 is a potent, selective inhibitor of the classical pathway of complement. Specificity for the active form of C1s was confirmed in a ligand binding assay. Finally, TNT010 (a precursor to SAR445088) was assessed in vitro for its ability to inhibit complement activation associated with cold agglutinin disease (CAD). TNT010 inhibited C3b/iC3b deposition on human red blood cells incubated with CAD patient serum and decreased their subsequent phagocytosis by THP-1 cells. In summary, this study identifies SAR445088 as a potential therapeutic for the treatment of classical pathway-driven diseases and supports its continued assessment in clinical trials.
本研究的目的是描述 SAR445088 的补体抑制活性，SAR445088 是一种针对 C1s 活性形式的新型单克隆抗体。Wieslab® 和溶血测定用于证明 SAR445088 是补体经典途径的有效、选择性抑制剂。在配体结合测定中证实了对 C1s 活性形式的特异性。最后，在体外评估了 TNT010（SAR445088 的前体）抑制与冷自身免疫性疾病（CAD）相关的补体激活的能力。TNT010 抑制了与 CAD 患者血清孵育的人红细胞上 C3b/iC3b 的沉积，并减少了随后 THP-1 细胞的吞噬作用。总之，本研究鉴定 SAR445088 作为一种治疗经典途径驱动疾病的潜在治疗方法，并支持其在临床试验中的进一步评估。
