Naturally developing cancers in animals can be used as models for human cancer treatment. The Biopharmaceutical Development Program successfully produced multiple antibodies for immuno-oncology targets for clinical trials. More antibodies are in the discovery stage.
Dogs spontaneously develop cancers that resemble human malignancies. These cancers have similarities in many important respects, including phenotype, histology, immune responses, mutational signatures, and signaling pathways. Canine cancer is an appealing model to rapidly evaluate and prioritize new immune-oncology agents and their combinations in clinical trials.
Cancer cells downregulate the activity of stimulatory immunoreceptors while upregulating the activity of inhibitory immunoreceptors of the immune cells. Several inhibitory immunoreceptors, referred to as check point inhibitors, have been identified and studied in cancer in past decades, such as PD-1, CTLA-4, LAG3, TIM3, TIGIT, and BTLA. Immune checkpoint signal modulation has become a major tool in fighting cancer. For evaluating cancer immunotherapies and drug combinations, the Biopharmaceutical Development Program is developing novel canine antibodies to multiple immuno-oncology targets.
Canine immuno-oncology pipeline
Multiple mouse and rabbit antibodies for immune oncology targets are in the discovery stage:
- CD40
- CD47
- LAG3
Clinical study antibodies
- Developed high affinity canine-CTLA mouse monoclonal antibody that can block the CTLA inhibitory signal. The chimeric and caninized versions anti-CTLA were made for clinical studies.
- Canine chimeric anti-CTLA4 mAbs were made by transient expression for in vivo trials.
- Stable cell lines for chimeric and canine anti-CTLA were generated. These antibodies are produced in large scale and vialed for clinical studies.
- Generated stable cell lines and produced canine chimeric anti-PDL1 monoclonal antibodies collaboration with Purdue University and the National Cancer Institute.
- Currently the safety studies are in progress for anti-CTLA and anti-PDL1 antibodies.
This work is funded by the National Cancer Institute Division of Cancer Treatment and Diagnosis and is part of the NCI Comparative Oncology Program and PRECINCT(PRE-medical Cancer Immunotherapy Network Canine Trials).