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为了赋予TNF-α抗体对炎症组织的特异性,构建了抗TNF-α/抗纤维连接蛋白额外域B(ED-B)的基因工程双特异抗体Bs Db。Bs Db在大肠杆菌中获得了高效表达,表达产物经鉴定、纯化和复性制备后,进行了生物学活性和药动学分析。Bs Db可同时结合重组人TNF-α和ED-B,并中和TNF-α生理作用。在胶原诱导的小鼠关节炎模型中,Bs Db快速从血浆和正常组织清除,但能选择性的积累和保留于炎症关节。说明Bs Db具有炎症组织的特异性和正常组织的低毒性,在类风湿关节炎和其他自身免疫性疾病的治疗上具有较大潜力,为其临床前期研究奠定了基础。
To confer specificity of TNF-α antibodies on inflammatory tissues, a genetically engineered bispecific antibody Bs Db was constructed against the anti-TNF-α / anti-fibronectin extra domain B (ED-B). Bs Db was highly expressed in E.coli. The expressed product was identified, purified and refolded. After biological activity and pharmacokinetic analysis, Bs Db was expressed. Bs Db binds both recombinant human TNF-α and ED-B simultaneously and neutralizes the physiological effects of TNF-α. In the collagen-induced mouse arthritis model, Bs Db is rapidly cleared from plasma and normal tissues but selectively accumulates and retains in the inflammatory joints. It shows that Bs Db possesses the characteristics of inflammatory tissue and low toxicity of normal tissue. It has great potential in the treatment of rheumatoid arthritis and other autoimmune diseases, which lays a foundation for its preclinical research.