Antigen Design for Successful Isolation of Highly Challenging Therapeutic Anti-GPCR Antibodies

Int J Mol Sci. 2020 Nov 3;21(21):8240. doi: 10.3390/ijms21218240.

Abstract

G-protein-coupled receptors (GPCR) transmit extracellular signals into cells to regulate a variety of cellular functions and are closely related to the homeostasis of the human body and the progression of various types of diseases. Great attention has been paid to GPCRs as excellent drug targets, and there are many commercially available small-molecule chemical drugs against GPCRs. Despite this, the development of therapeutic anti-GPCR antibodies has been delayed and is challenging due to the difficulty in preparing active forms of GPCR antigens, resulting from their low cellular expression and complex structures. Here, we focus on anti-GPCR antibodies that have been approved or are subject to clinical trials and present various technologies to prepare active GPCR antigens that enable the isolation of therapeutic antibodies to proceed toward clinical validation.

Keywords: G protein-coupled receptor; antigen; membrane protein; therapeutic antibody.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / isolation & purification*
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Antibody Specificity
  • Antigens* / chemistry
  • Antigens* / immunology
  • Drug Design*
  • Epitope Mapping / methods
  • Humans
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Receptors, G-Protein-Coupled