Pharmacokinetics of anti-IL17A and anti-IL22 peptide-antibody bispecific genetic fusions in mice

详细信息    查看全文

• 作者：Yulia Vugmeyster ; Yiqun (Etran) Zhang ; Xiaotian Zhong ; Jill Wright ; Sheldon S. Leung
• 关键词：Bi-specific ; Bi-functional pharmacokinetics ; Genetic fusion ; Peptide ; Antibody
• 刊名：International Immunopharmacology
• 出版年：February, 2014
• 年：2014
• 卷：18
• 期：2
• 页码：225-227
• 全文大小：248 K

文摘

The peptide-antibody (Ab) genetic fusion is a promising technology for targeting multiple antigens in a single Ab-like molecule. We have recently described generation and in vitro characterization of several such genetic fusions, using an interleukin (IL)-17A binding peptide and an anti-IL-22 Ab as a model system. In this study we assessed pharmacokinetic profiles of these model genetic fusions in mice. Specifically an IL-17A binding peptide was fused to either the heavy chain or both the heavy and the light chains of an anti-IL22 human IgG1 (referred to Compounds 1 or 2, respectively). Swiss Webster mice were given a single 10 mg/kg IV dose of Compound 1 or Compound 2 and serum concentrations were measured by a fused molecule immunoassay, in which IL-17A was used as a capture and anti-human IgG was used as a detector. In addition, serum samples were assayed using a total human IgG immunoassay. PK parameters were calculated by non-compartmental modeling. The two genetic fusions had similar PK profiles, with total body clearance of ~ 0.9-1.0 mL/h/kg, volume of distribution at steady-state of ~ 63-65 mL/kg, and elimination half-life of ~ 40 h. Our study provides the first characterization of the PK properties of peptide-Ab genetic fusions and suggests that although these genetic fusions appear to be eliminated faster than a typical Ab, the PK profile may be suitable for preclinical and clinical testing.