Most cited article - PubMed ID 36551672
Development of Monoclonal Antibodies Targeting Canine PD-L1 and PD-1 and Their Clinical Relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma
Monoclonal antibodies targeting immune checkpoints have revolutionized oncology. Yet, the effectiveness of these treatments varies significantly among patients, and they are associated with unexpected adverse events, including hyperprogression. The murine research model used in drug development fails to recapitulate both the functional human immune system and the population heterogeneity. Hence, a novel model is urgently needed to study the consequences of immune checkpoint blockade. Dogs appear to be uniquely suited for this role. Approximately 1 in 4 companion dogs dies from cancer, yet no antibodies are commercially available for use in veterinary oncology. Here we characterize two novel antibodies that bind canine PD-1 with sub-nanomolar affinity as measured by SPR. Both antibodies block the clinically crucial PD-1/PD-L1 interaction in a competitive ELISA assay. Additionally, the antibodies were tested with a broad range of assays including Western Blot, ELISA, flow cytometry, immunofluorescence and immunohistochemistry. The antibodies appear to bind two distinct epitopes as predicted by molecular modeling and peptide phage display. Our study provides new tools for canine oncology research and a potential veterinary therapeutic.
- Keywords
- PD-1, PD-L1, cancer immunotherapy, canine cancer, comparative oncology, immune checkpoint, monoclonal antibody, veterinary oncology,
- MeSH
- B7-H1 Antigen immunology antagonists & inhibitors metabolism MeSH
- Programmed Cell Death 1 Receptor * antagonists & inhibitors immunology MeSH
- Epitopes immunology MeSH
- Immune Checkpoint Inhibitors immunology pharmacology MeSH
- Humans MeSH
- Antibodies, Monoclonal * immunology MeSH
- Neoplasms immunology veterinary drug therapy MeSH
- Dog Diseases immunology drug therapy MeSH
- Dogs * MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Dogs * MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- Names of Substances
- B7-H1 Antigen MeSH
- Programmed Cell Death 1 Receptor * MeSH
- Epitopes MeSH
- Immune Checkpoint Inhibitors MeSH
- Antibodies, Monoclonal * MeSH
