Abstract 2234: Development of caninized monoclonal antibodies against PD1

Abstract

Abstract Immune blockade of inhibitory immune checkpoint (IC) mediated by Programmed cell death protein 1 (PD1) significantly increases survival of patients with advanced melanoma and other cancers. Dogs constitute a unique model for studying cancer types relevant to humans. Canine malignancies occur spontaneously and share many pathogenic pathways as well as therapy responses with their human counterparts. Dogs have a fully functional immune system, share the owners' lifestyle, environmental exposures, and their genome is more similar to the human one than the murine one is. Canine cancer research may be a superior alternative to mouse studies in the context of immunotherapy development. Unfortunately, IC-blocking antibodies are not available for companion animals. Monoclonal antibody against canine ICs has been previously developed by our group using mouse hybridoma technology. While functional, it couldn't be used clinically due to immunogenicity. To create a viable therapeutic, the antibody sequence was caninized. The murine constant regions of heavy and light chains were substituted with corresponding canine sequences. Following that, the variable regions' structural frameworks were replaced with canine sequences generated based on a canine library of antibody sequences.Additionally, we developed an antibody against the PDL1 protein using a previously established canine antibody phage library. The PD1 and PDL1 antibodies are being characterized by ELISA and cell-based blocking assays, T-cell activation assays and growth assessment of the impact on spheroid growth in patient-derived cultures.The characterized antibodies will widen the availability of canine IC blockers and pave the path for further research in comparative oncology. Citation Format: Mikolaj Kocikowski, Katarzyna Dziubek, Borek Vojtesek, David Argyle, Ted Hupp, Maciej Parys. Development of caninized monoclonal antibodies against PD1 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2234.