Development of canine PD-1/PD-L1 specific monoclonal antibodies and amplification of canine T cell function

Jin Wook Choi, Sita S. Withers, Hong Chang, Justin A. Spanier, Victoria L. De La Trinidad, Harmanpreet Panesar, Brian T. Fife, Roger Sciammas, Ellen Elizabeth Sparger, Peter F. Moore, Michael S Kent, Robert B Rebhun, Stephen J Mcsorley

Research output: Contribution to journalArticle

Abstract

Interruption of the programmed death 1 (PD-1) / programmed death ligand 1 (PD-L1) pathway is an established and effective therapeutic strategy in human oncology and holds promise for veterinary oncology. We report the generation and characterization of monoclonal antibodies specific for canine PD-1 and PD-L1. Antibodies were initially assessed for their capacity to block the binding of recombinant canine PD-1 to recombinant canine PD-L1 and then ranked based on efficiency of binding as judged by flow cytometry. Selected antibodies were capable of detecting PD-1 and PD-L1 on canine tissues by flow cytometry and Western blot. Anti-PD-L1 worked for immunocytochemistry and anti-PD-1 worked for immunohistochemistry on formalin-fixed paraffin embedded canine tissues, suggesting the usage of this antibody with archived tissues. Additionally, anti-PD-L1 (JC071) revealed significantly increased PD-L1 expression on canine monocytes after stimulation with peptidoglycan or lipopolysaccharide. Together, these antibodies display specificity for the natural canine ligand using a variety of potential diagnostic applications. Importantly, multiple PD-L1-specific antibodies amplified IFN-γ production in a canine peripheral blood mononuclear cells (PBMC) concanavlin A (Con A) stimulation assay, demonstrating functional activity.

Original languageEnglish (US)
Pages (from-to)e0235518
JournalPloS one
Volume15
Issue number7
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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