Development of functional mutant protein with antagonistic activity as an anti-inflammatory drug

阻断TNF与TNF受体亚型1（TNFR 1）的结合被认为是治疗自身免疫性疾病的有希望的策略。最近，我们利用噬菌体展示技术获得了具有拮抗活性的TNFR 1选择性突变TNF（R1 antTNF）。在这项研究中，R1 antTNF的抗炎作用进行了研究。首先，为了提高体内稳定性，制备了聚乙二醇修饰的R1 antTNF（PEG-R1 antTNF）。在自身免疫性疾病模型中，给予PEG-R1 antTNF的小鼠的临床评分得到改善。这些结果表明，选择性阻断TNFR 1的PEG-R1 antTNF可能是一种有效的治疗策略，对自身免疫性疾病。

Blocking the binding of TNF to TNF receptor subtype 1 (TNFR1) is believed to be a promising strategy for the treatment of autoimmune disease. Recently, we generated the TNFR1-selective mutant TNF with antagonistic activity (R1antTNF) using phage display technique. In this study, the anti-inflammatory effects of R1antTNF have been investigated. First, to improve the in vivo stability, polyethylene glycol-modified R1antTNF (PEG-R1antTNF) was prepared. In the autoimmune disease model, the clinical score of the mice given PEG-R1antTNF was improved. These results suggest that selective blocking of TNFR1 by PEG-R1antTNF could be an effective therapeutic strategy against autoimmune disease.