peptibody

A peptibody is a recombinant fusion protein that combines a peptide ligand with an antibody-based scaffold. Typically the peptide is fused to an IgG Fc region or to an antibody fragment, producing a molecule that retains the targeting features of the peptide and the pharmacokinetic and effector properties of an antibody.

The most common designs place a short peptide sequence at the N- or C-terminus of an Fc domain or at the C-terminus of an antibody chain, connected by flexible linkers. Some variants use single-chain antibody fragments (scFv) or Fab fragments as scaffolds. Peptibodies are produced by standard recombinant expression in mammalian cells, enabling proper folding and glycosylation.

By fusing a targeting peptide to an Fc-containing scaffold, peptibodies gain increased serum half-life through FcRn recycling and can demonstrate avidity through multivalent presentation. They can be designed to block receptor signaling, recruit immune effector functions, or deliver payloads to specific cells. The approach combines the selectivity of peptides with the stability and manufacturability of antibody-based biologics.

Peptibodies have been explored as therapeutics, diagnostics, and research tools, including targets in cancer, metabolic receptors, and imaging agents. Advantages include improved stability, longer circulating exposure, and potential for straightforward scale-up for some designs. Challenges include potential immunogenicity, manufacturing complexity, and the need for robust in vivo validation and regulatory assessment.