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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Characterization of Anti-Canine PD-1 Antibodies
Colin J Hartman1, Petra Sergent1, Anna Barbara Emilia Zimmermann2,3
1Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, 621 Rubin Building-HB7936, 1 Medical Center Drive, Lebanon, NH 03756, USA.
Abstract:
Cancer is a leading cause of death in dogs, and incidence rates in dogs exceed those in humans. Current therapeutic options for canine cancer patients remain limited, with most treatments focused on palliative care. Immune checkpoint inhibitors such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies that have transformed cancer therapy and expanded the therapeutic options in humans could offer the same clinical benefit in canine cancer patients. This study details the engineering and functional characterization of mouse and chimeric mouse-canine anti-canine PD-1 (cPD-1) monoclonal antibodies. We demonstrate that anti-cPD-1 antibodies block the interaction between cPD-1 and its ligand cPD-L1, thereby inhibiting this immune signaling pathway. In a proof-of-concept study in seven companion canine cancer patients, intratumoral therapy with the lead anti-cPD-1 antibody (HugPetmab) was safe, well-tolerated, had no observed adverse events, and showed evidence of tumor control in a subset of injected tumors. These findings support the potential of HugPetmab antibody as an immunotherapeutic option for treating canine cancer patients.
Insights
New canine cancer immunotherapies show promise. Anti-canine PD-1 antibodies were engineered and tested, demonstrating safety and tumor control in a small study, offering hope for better canine cancer treatments.
Area of Science:
- Veterinary Oncology
- Immunotherapy
- Canine Cancer Research
Background:
- Canine cancer is a significant cause of death, with limited therapeutic options.
- Human cancer therapies like immune checkpoint inhibitors have transformed treatment outcomes.
- Exploring similar immunotherapeutic strategies for dogs could improve clinical benefits.
Purpose of the Study:
- To engineer and characterize mouse and chimeric mouse-canine anti-canine PD-1 (cPD-1) monoclonal antibodies.
- To evaluate the safety and efficacy of these antibodies in canine cancer patients.
- To assess the potential of anti-cPD-1 antibodies as a novel immunotherapeutic approach for dogs.
Main Methods:
- Development of monoclonal antibodies targeting canine PD-1 (cPD-1).
- Functional characterization of antibody-mediated blockade of the cPD-1/cPD-L1 immune signaling pathway.
- Proof-of-concept intratumoral therapy in seven companion canine cancer patients using HugPetmab.
Main Results:
- Engineered anti-cPD-1 antibodies successfully blocked the cPD-1/cPD-L1 interaction.
- Intratumoral therapy with HugPetmab was safe and well-tolerated in canine patients.
- Evidence of tumor control was observed in a subset of treated tumors.
Conclusions:
- Anti-cPD-1 antibodies hold potential as a novel immunotherapeutic strategy for canine cancer.
- HugPetmab demonstrated safety and preliminary efficacy, supporting its further development.
- This research paves the way for expanded immunotherapeutic options in veterinary oncology.
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