Live long and active: Polypeptide-mediated assembly of antibody variable fragments

Adv Drug Deliv Rev. 2020 Dec:167:1-18. doi: 10.1016/j.addr.2020.10.017. Epub 2020 Oct 28.

Abstract

Antibodies possess multiple biologically relevant features that have been engineered into new therapeutic formats. Two examples include the adaptable specificity of their variable (Fv) region and the extension of plasma circulation times through their crystallizable (Fc) region. Since the invention of the single chain variable fragment (scFv) in 1988, antibody variable regions have been re-engineered into a wide variety of multifunctional nanostructures. Among these strategies, peptide-mediated self-assembly of variable regions through heterologous expression has become a powerful method to produce homogenous, functional biomaterials. This manuscript reviews recent reports of antibody fragments assembled through fusion with peptides and proteins, including elastin-like polypeptides (ELPs), collagen-like polypeptides (CLPs), albumin, transmembrane proteins, leucine zippers, silk protein, and viruses. This review further discusses the current clinical status of engineered antibody fragments and challenges to overcome.

Keywords: Albumin; Antibody engineering; Collagen-like polypeptides; Elastin-like polypeptides; Exosome; Fibroin; Leucine zipper; SpyCatcher-SpyTag; Virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Albumins / chemistry
  • Antibodies / immunology*
  • Biomedical Engineering / methods*
  • Collagen / chemistry
  • Drug Delivery Systems / methods*
  • Humans
  • Nanostructures / chemistry*
  • Peptides / chemistry
  • Proteins / chemistry
  • Single-Chain Antibodies / immunology*
  • Viral Proteins

Substances

  • Albumins
  • Antibodies
  • Peptides
  • Proteins
  • Single-Chain Antibodies
  • Viral Proteins
  • Collagen