Anti-serum albumin domain antibodies in the development of highly potent, efficacious and long-acting interferon

Protein Eng Des Sel. 2010 Apr;23(4):271-8. doi: 10.1093/protein/gzp091. Epub 2010 Jan 21.

Abstract

Serum albumin-binding domain antibodies (AlbudAbs) have previously been shown to greatly extend the serum half-life of the interleukin-1 receptor antagonist IL-1ra. We have subsequently extended this approach to look at the in vitro activity, in vivo efficacy and pharmacokinetics of an agonist molecule, interferon (IFN)-alpha2b, fused to an AlbudAb. Here we describe this molecule and show that in this format AlbudAb half-life extension technology displays significant advantages in comparison with other methods of half-life extension, in particular genetic fusion to serum albumin. When compared directly IFN-alpha2b fused to an Albudab shows higher potency, increased serum half-life and greater efficacy than human serum albumin fused to IFN-alpha2b. AlbudAbs are therefore an ideal platform technology for creation of therapeutics with agonist activity and long serum half-lives.

MeSH terms

  • Antibodies / chemistry
  • Antibodies / genetics*
  • Antibodies / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / chemistry
  • Interferon-alpha / pharmacokinetics*
  • Interferon-alpha / pharmacology
  • Protein Engineering / methods
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Proteins
  • Serum Albumin / chemistry
  • Serum Albumin / immunology*
  • Surface Plasmon Resonance
  • Tumor Cells, Cultured

Substances

  • Antibodies
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Serum Albumin