Comparative characterization of two monoclonal antibodies targeting canine PD-1

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/PDL1 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.