Development of a next-generation antibody drug for canine tumors that blocks an immune checkpoint molecule

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K14983
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Hokkaido University
• Principal Investigator: Maekawa Naoya 北海道大学, 獣医学研究院, 特任助教 (70829035)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 獣医学 / 免疫学 / 腫瘍免疫 / 小動物（イヌ） / 免疫チェックポイント阻害薬 / 抗体薬 / 免疫療法

Outline of Final Research Achievements

In this study, we developed a novel antibody drug candidate based on a conventional immune checkpoint inhibitor (anti-PD-L1 antibody) as a novel immunotherapy for canine tumors, and evaluated its function. First, we analyzed immune-related molecules which is associated with the therapeutic efficacy of anti-PD-L1 therapy, and identified several candidate factors. We developed an inhibitor for one of such immunosuppressive factors and prepared a new antibody drug candidate in combination with an anti-PD-L1 antibody. We found that the new candidate successfully activated canine immune cells, and no safety problems were observed with its repeated administration to a laboratory dog. This research has advanced the technology for developing antibody drugs for dogs, and has paved the way for their clinical application.

Free Research Field

獣医学

Academic Significance and Societal Importance of the Research Achievements

本研究で同定した免疫チェックポイント阻害薬の効果に関連のある因子群は、同治療に対する抵抗性因子である可能性があり今後治療標的として併用治療法の開発につながる可能性がある。また、本研究で検討したイヌ用抗体薬の作製技術はイヌに対する抗体医薬開発のモデルケースとなり、動物用抗体薬開発の発展につながると考えられる。イヌ腫瘍はヒト腫瘍のモデル疾患ともなりうることから、イヌ腫瘍における新規治療法の有効性や安全性等の情報は、医薬品開発にも有用である可能性がある。