Search of novel therapeutic candidate drugs targeting bone marrow-derived suppressor cells in tumor-bearing dogs

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Tamura Kyoichi 日本獣医生命科学大学, 獣医学部, 講師 (00722282)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 犬 / がん / 骨髄由来抑制細胞 / 免疫抑制 / キナーゼ阻害剤 / がん免疫療法

Outline of Final Research Achievements

As a result of the experiments shown in the research plan, CD11b+Gr-1+ cells could be efficiently induced to differentiate from canine bone marrow mononuclear cells by culturing canine bone marrow mononuclear cells in the presence of GM-CSF and IL-6, and then adding the supernatant of tumor-derived cell lines. In addition, cells induced to differentiate by this method possessed immunosuppressive factors such as arginase activity, NO and ROS, which are characteristic features of MDSC. The method of inducing differentiation of MDSCs using canine bone marrow cells established in this study may be useful in the future search for new candidate drugs for the treatment of malignant tumors in dogs.

Free Research Field

獣医学関連

Academic Significance and Societal Importance of the Research Achievements

本研究により確立した犬のMDSCの分化誘導法により、大量に精製するのが困難な担癌犬生体内のMDSCを再現した細胞を簡便に培養することが可能となった。この成果に基づいて、犬の骨髄細胞と種々の株化腫瘍細胞を用いてMDSCを分化誘導し、キナーゼ阻害剤によるMDSCのT細胞増殖抑制への影響を検討することで、種々のがんに対しキナーゼ阻害剤を用いたMDSCの免疫抑制機能制御を目的とした新規治療法の開発に寄与することが期待される。