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Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a
Min-Young Song1,2, Jaewon Cho1, Hyosung Park1
1Department of Pharmacy, Kangwon National University, Chuncheon, 24341, Republic of Korea.
Abstract:
Targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is promising in treating cancer in humans and offers potential for veterinary applications. However, no PD-L1 antibodies have been approved specifically for treating canine cancer. We aimed to develop PD-L1-specific antibodies using phage display technology for treating canine cancer. A synthetic antibody library was screened, and 18 high-affinity single-chain variable fragment clones were subsequently converted to the IgG format for enhancing binding affinity and functional stability. The clone #15 exhibited the highest binding affinity and most pronounced antitumor effects. The PD-1/PD-L1 interaction was inhibited by antibody #15. The binding and thermal stabilities of the antibodies were validated by flow cytometry and thermal stability assays, respectively. In NOG mice xenografted with canine osteosarcoma cells and treated with canine peripheral blood mononuclear cells and antibody #15, the tumor size and weight were reduced. Antibody #15 significantly increased apoptosis of tumor cells and lymphocyte populations. Therefore, anti-PD-L1 antibodies, particularly antibody #15, have substantial potential as novel immunotherapeutic agents against canine osteosarcoma. This study represents a significant advancement in veterinary oncology, with the potential of improving treatment outcomes for canine cancers and providing insights into similar strategies in human cancer therapy.
Insights
Researchers developed a novel antibody targeting programmed cell death ligand 1 (PD-L1) for canine cancer. This antibody, #15, demonstrated significant antitumor effects in preclinical models, offering new hope for veterinary oncology.
Area of Science:
- Veterinary Oncology
- Immunotherapy
- Antibody Engineering
Background:
- The programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is a key target in cancer immunotherapy.
- While effective in human medicine, no PD-L1 antibodies are approved for canine cancer treatment.
- Developing targeted therapies for canine cancers is a critical unmet need.
Purpose of the Study:
- To develop and characterize novel PD-L1-specific antibodies for treating canine cancer.
- To evaluate the therapeutic potential of these antibodies in preclinical canine osteosarcoma models.
Main Methods:
- Phage display technology was used to screen a synthetic antibody library.
- High-affinity single-chain variable fragment (scFv) clones were converted to IgG format.
- In vivo efficacy was assessed using a xenograft mouse model with canine osteosarcoma cells, peripheral blood mononuclear cells, and the lead antibody candidate.
Main Results:
- Antibody #15 demonstrated high binding affinity and inhibited the PD-1/PD-L1 interaction.
- Treatment with antibody #15 significantly reduced tumor size and weight in xenografted mice.
- Antibody #15 promoted tumor cell and lymphocyte apoptosis, indicating an immunotherapeutic effect.
Conclusions:
- Novel anti-PD-L1 antibodies, particularly antibody #15, show significant potential as immunotherapeutic agents for canine osteosarcoma.
- This research advances veterinary oncology and may offer insights for human cancer therapy strategies.
