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Development of an Anti-canine PD-L1 Antibody and Caninized PD-L1 Mouse Model as Translational Research Tools for the
Wonkyung Oh1, Alyssa Min Jung Kim1, Deepika Dhawan2
1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana.
Abstract:
Immune checkpoint blockade therapy, one of the most promising cancer immunotherapies, has shown remarkable clinical impact in multiple cancer types. Despite the recent success of immune checkpoint blockade therapy, however, the response rates in patients with cancer are limited (∼20%-40%). To improve the success of immune checkpoint blockade therapy, relevant preclinical animal models are essential for the development and testing of multiple combination approaches and strategies. Companion dogs naturally develop several types of cancer that in many respects resemble clinical cancer in human patients. Therefore, the canine studies of immuno-oncology drugs can generate knowledge that informs and prioritizes new immuno-oncology therapy in humans. The challenge has been, however, that immunotherapeutic antibodies targeting canine immune checkpoint molecules such as canine PD-L1 (cPD-L1) have not been commercially available. Here, we developed a new cPD-L1 antibody as an immuno-oncology drug and characterized its functional and biological properties in multiple assays. We also evaluated the therapeutic efficacy of cPD-L1 antibodies in our unique caninized PD-L1 mice. Together, these in vitro and in vivo data, which include an initial safety profile in laboratory dogs, support development of this cPD-L1 antibody as an immune checkpoint inhibitor for studies in dogs with naturally occurring cancer for translational research. Our new therapeutic antibody and caninized PD-L1 mouse model will be essential translational research tools in raising the success rate of immunotherapy in both dogs and humans.
Significance:
Our cPD-L1 antibody and unique caninized mouse model will be critical research tools to improve the efficacy of immune checkpoint blockade therapy in both dogs and humans. Furthermore, these tools will open new perspectives for immunotherapy applications in cancer as well as other autoimmune diseases that could benefit a diverse and broader patient population.
Insights
Researchers developed a novel canine PD-L1 antibody and a specialized mouse model to advance cancer immunotherapy. These tools aim to improve immune checkpoint blockade therapy success rates in both dogs and humans, aiding translational research.
Area of Science:
- Oncology
- Immunology
- Translational Medicine
Background:
- Immune checkpoint blockade therapy shows promise but has limited response rates.
- Preclinical models are crucial for developing combination immunotherapies.
- Canine cancers resemble human cancers, making dogs valuable models for immuno-oncology drug development.
Purpose of the Study:
- To develop and characterize a novel canine PD-L1 antibody for immuno-oncology.
- To evaluate the therapeutic efficacy of the canine PD-L1 antibody in a caninized mouse model.
- To establish essential translational research tools for improving cancer immunotherapy.
Main Methods:
- Development and functional characterization of a canine PD-L1 antibody.
- Evaluation of antibody efficacy in caninized PD-L1 mice.
- Initial safety profiling in laboratory dogs.
Main Results:
- A novel canine PD-L1 antibody with characterized functional and biological properties was developed.
- Therapeutic efficacy of the canine PD-L1 antibody was demonstrated in caninized PD-L1 mice.
- The antibody and mouse model show potential as translational research tools.
Conclusions:
- The developed canine PD-L1 antibody and caninized mouse model are valuable tools for advancing cancer immunotherapy research.
- These tools can help improve the success rates of immune checkpoint blockade therapy in dogs and humans.
- The research opens new avenues for immunotherapy in cancer and autoimmune diseases.
