Novel antibody therapy targeting tumor specific sugar-chain modification in tumor cells and cancer associated fibroblasts

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22361
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Nishimura Ryohei 東京大学, 大学院農学生命科学研究科(農学部), 教授 (80172708)
• Co-Investigator(Kenkyū-buntansha): 加藤 幸成 東北大学, 未来科学技術共同研究センター, 教授 (00571811)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 犬 / 固形腫瘍 / 抗体療法 / ポドプラニン / 腫瘍関連線維芽細胞

Outline of Final Research Achievements

Solid tumors are composed of not only tumor cells but also various cells such as blood vessels, immune cells, and cancer-associated fibroblasts (CAF), but a therapy targeting CAF has not yet been established. In this study, we prepared a canine chimeric anti-podoplanin cytotoxic antibody that can simultaneously target CAF and tumor cells, and successfully demonstrated efficacy and safety of this antibody by experiments of canine tumor cell lines, canine tumor inoculated mouse models, and cancer-bearing dog cases. We conducted the clinical trial using this antibody and obtained data suggesting the efficacy and safety of this antibody. In clinical trials involving a small number of dog cases, reactions suggesting antitumor effects were observed without serious side effects, and these data support the further large-scale clinical trials in the future.

Free Research Field

獣医学

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍は、犬・猫・人において主要な死亡原因であり、その克服は社会的な重要課題である。本研究では、悪性腫瘍のなかでも固形腫瘍に特有の腫瘍関連線維芽細胞および腫瘍細胞を同時に標的にできる抗体療法の安全性および有効性を実証することで、腫瘍治療学の発展に大きく貢献した。また、本研究では症例犬の臨床試験にも成功し、臨床獣医学における新たな腫瘍治療法の基盤となる重要な成果を報告できた。