Recombinant Anti-idiotypic Antibodies in Ligand Binding Assays for Antibody Drug Development

Methods Mol Biol. 2021:2261:291-306. doi: 10.1007/978-1-0716-1186-9_18.

Abstract

Sensitive and reproducible pharmacokinetic (PK) assays and immunogenicity assessment are required as part of the complex and lengthy development process for biotherapeutic proteins. Ligand binding assays (LBAs) are included in a range of approaches applied to understand the nature and properties of the drug as well as the induction of anti-drug antibodies (ADA) against the therapeutic, which can cause adverse events and loss of efficacy. Currently, most biotherapeutics are monoclonal human or humanized antibodies. Anti-idiotypic antibodies, targeting the idiotopic determinants of individual antibody drugs are recognized as perfect reagents for such LBAs. Here we describe the typical setups for these assays and how different types of anti-biotherapeutic antibodies can be used to establish selective and sensitive assays.

Keywords: Anti-biotherapeutic antibody; Anti-drug antibody; Anti-idiotypic antibody; HuCAL; Immunogenicity assay; Ligand binding assay; Pharmacokinetic analysis.

MeSH terms

  • Antibodies, Anti-Idiotypic / immunology*
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibody Specificity
  • Biological Products / immunology*
  • Biological Products / pharmacokinetics
  • Drug Development*
  • Drug Monitoring*
  • Epitopes*
  • Humans
  • Immunoassay*
  • Immunoglobulin Idiotypes
  • Ligands
  • Protein Binding
  • Proteins / immunology*
  • Proteins / pharmacokinetics

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Humanized
  • Biological Products
  • Epitopes
  • Immunoglobulin Idiotypes
  • Ligands
  • Proteins