title: Plasma half-life extension of small recombinant antibodies by fusion to immunoglobulin-binding domains.
abstract: Many therapeutic proteins possessing a small size are rapidly cleared from circulation. Half-life extension strategies have therefore become increasingly important to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. Here, we performed a comparative analysis of the half-life extension properties of various bacterial immunoglobulin-binding domains (IgBDs) derived from Staphylococcus protein A (SpA), Streptococcus protein G (SpG), and Finegoldia (formerly Peptostreptococcus) protein L (PpL). These domains, composed of 50-60 amino acid residues, were fused to the C terminus of a single-chain Fv and a bispecific single-chain diabody, respectively. All fusion proteins were produced in mammalian cells and retained their antigen-binding properties. The half-lives of the antibody molecules were prolonged to varying extents for the different IgBDs. The strongest effects in mice were observed for domain C3 of SpG (SpG(C3)) followed by domains B and D of SpA, suggesting that SpG(C3) is particularly useful to extend the plasma half-life of small proteins.
authors.affiliation: Institut für Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Hutt
authors.forename: Aline
authors.initials: A
authors.lastname: Färber-Schwarz
authors.forename: Felix
authors.initials: F
authors.lastname: Unverdorben
authors.forename: Fabian
authors.initials: F
authors.lastname: Richter
authors.forename: Roland E
authors.initials: RE
authors.lastname: Kontermann
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000493:pharmacokinetics* / Q000494:pharmacology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies