Design and characterization of mouse IgG1 and IgG2a bispecific antibodies for use in syngeneic models

MAbs. 2020 Jan-Dec;12(1):1685350. doi: 10.1080/19420862.2019.1685350.

Abstract

The development of antibody therapeutics relies on animal models that accurately recapitulate disease biology. Syngeneic mouse models are increasingly used with new molecules to capture the biology of complex cancers and disease states, and to provide insight into the role of the immune system. The establishment of syngeneic mouse models requires the ability to generate surrogate mouse counterparts to antibodies designed for humans. In the field of bispecific antibodies, there remains a dearth of technologies available to generate native IgG-like mouse bispecific antibodies. Thus, we engineered a simple co-expression system for one-step purification of intact mouse IgG1 and IgG2a bispecific antibodies from any antibody pair. We demonstrated proof of concept with CD3/CD20 bispecific antibodies, which highlighted both the quality and efficacy of materials generated by this technology.

Keywords: Mouse bispecific antibodies; T-cell engaging bispecific antibody; co-expression; electrostatic steering; inter-chain disulfide bond shifting; syngeneic mouse model.

MeSH terms

  • Animals
  • Antibodies, Bispecific / genetics*
  • Antibodies, Bispecific / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CHO Cells
  • Cloning, Molecular
  • Cricetulus
  • Disease Models, Animal
  • Immunoglobulin G / genetics*
  • Immunoglobulin G / metabolism
  • Mice
  • Protein Binding
  • Protein Conformation
  • Protein Engineering / methods*
  • Rituximab / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transplantation, Isogeneic

Substances

  • Antibodies, Bispecific
  • CD3 Complex
  • Immunoglobulin G
  • Rituximab