一种P-选择素介导的滚动的高亲和力人源抗体拮抗剂。
A high affinity human antibody antagonist of P-selectin mediated rolling.
作者信息
Swers Jeffrey S, Widom Angela, Phan Uyen, Springer Timothy A, Wittrup K Dane
机构信息
Department of Chemical Engineering, Massachusetts Institute of Technology 66-552, 25 Ames Street, Cambridge, MA 02139, USA.
出版信息
Biochem Biophys Res Commun. 2006 Nov 24;350(3):508-13. doi: 10.1016/j.bbrc.2006.08.197. Epub 2006 Sep 28.
We have characterized the IgG form of a previously isolated and engineered single-chain Fv (scFv), named RR2r3s4-1, that binds to human PSGL-1. This fully human IgG was determined to have a Kd of 1.8+/-0.7 nM by fluorescence quenching titration. It better inhibits P-selectin-PSGL-1 interactions than a commercially available murine monoclonal antibody KPL1 and better inhibits neutrophil rolling than KPL1. Thus, RR2r3s4-1 is the most effective antibody at inhibiting P-selectin-PSGL-1 interactions known. Specificity analysis reveals that RR2r3s4-1 does not cross react with murine PSGL-1 and thus requires more than tyrosine sulfate for binding to human PSGL-1. This evidence demonstrates the therapeutic potential of this antibody as a potent anti-inflammatory therapeutic.
我们已经对一种先前分离并工程化的单链Fv（scFv）的IgG形式进行了表征，该单链Fv名为RR2r3s4-1，可与人PSGL-1结合。通过荧光猝灭滴定法测定，这种完全人源化的IgG的解离常数（Kd）为1.8±0.7 nM。与市售鼠单克隆抗体KPL1相比，它能更好地抑制P-选择素与PSGL-1的相互作用，并且比KPL1能更好地抑制中性粒细胞滚动。因此，RR2r3s4-1是已知的抑制P-选择素与PSGL-1相互作用最有效的抗体。特异性分析表明，RR2r3s4-1与鼠PSGL-1不发生交叉反应，因此其与人PSGL-1结合需要的不仅仅是硫酸酪氨酸。这一证据证明了这种抗体作为一种有效的抗炎治疗药物的治疗潜力。
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