Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms

PLoS One. 2020 Jul 16;15(7):e0235815. doi: 10.1371/journal.pone.0235815. eCollection 2020.

Abstract

Monoclonal antibodies (mAbs) for therapeutic applications should be as similar to native human antibodies as possible to minimize their immunogenicity in patients. Several transgenic animal platforms are available for the generation of fully human mAbs. Attributes such as specificity, efficacy and Chemistry, Manufacturing and Controls (CMC) developability of antibodies against a specific target are typically established for antibodies obtained from one platform only. In this study, monoclonal antibodies (mAbs) cross-reactive against human and cynomolgus LAMP1 were derived from the human immunoglobulin transgenic TRIANNI mouse and OmniChicken® platforms and assessed for their specificity, sequence diversity, ability to bind to and internalize into tumor cells, expected immunogenicity and CMC developability. Our results show that the two platforms were complementary at providing a large diversity of mAbs with respect to epitope coverage and antibody sequence diversity. Furthermore, most antibodies originating from either platform exhibited good manufacturability characteristics.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Chickens
  • Epitopes / immunology*
  • HEK293 Cells
  • Humans
  • Immunization
  • Lysosomal Membrane Proteins / immunology*
  • Macaca fascicularis
  • Mice
  • Models, Molecular

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • LAMP1 protein, human
  • Lysosomal Membrane Proteins

Grants and funding

Sanofi provided support in the form of salaries for BC, TD, LBS, MG, IA AS, FS, KR & TB, Ligand provided support in the form of salaries for JM, PAL, WH & KC, Carterra provided support in the form of salaries for YA. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.