Development of the combined immune-modulatory therapies for canine cancer

• Project/Area Number: 15H04598
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Yamaguchi University
• Principal Investigator: MIZUNO TAKUYA 山口大学, 共同獣医学部, 教授 (90398826)
• Co-Investigator(Kenkyū-buntansha): 富張 瑞樹 帯広畜産大学, 畜産学部, 准教授 (00552754) ; 中川 貴之 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (40447363)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: dog / cancer / immune checkpoint / oncolytic virotherapy / DNA vaccine / 犬 / 腫瘍 / 免疫 / ガン / 治療 / レオウイルス

Outline of Final Research Achievements

In this study, several clinical trials, such as oncolytic virotherapy using reovirus, DNA vaccine therapy, and PD-1 chimeric antibody therapy for canine cancer had been accomplished. Nineteen dogs with various tumors were enrolled for oncolytic virotherapy, which were evaluated. Several dogs showed clinical improvement. As as DNA vaccination therapy, novel adjuvant therapy had not established using mice model, but clinical trials had been done, and showed two dogs with malignant melanoma survived for more than 2 years. Regarding immunecheckpoint antibody therapy, PD-1 chimeric antibody therapy had been established based on monoclonal antibody against canine PD-1, which was developed in our laboratory and now has been evaluated for cancer-bearing dogs.

Research Products

• [Journal Article] Development and characterization of monoclonal antibodies against canine PD-1 and PD-L1. (2018)
  • Author(s): Nemoto Y, Shosu K, Okuda M, Noguchi S, Mizuno T.
  • Journal Title: Vet Immunol Immunopathol Volume: 198 Pages: 19-25
  • DOI: 10.1016/j.vetimm.2018.02.007
  • Peer Reviewed / Open Access
• [Journal Article] Oncolytic reovirus therapy: Pilot study in dogs with spontaneously occurring tumours. (2018)
  • Author(s): Hwang CC, Igase M, Sakurai M, Haraguchi T, Tani K, Itamoto K, Shimokawa T, Nakaichi M, Nemoto Y, Noguchi S, Coffey M, Okuda M, Mizuno T.
  • Journal Title: Vet Comp Oncol. Volume: - Issue: 2 Pages: 229-238
  • DOI: 10.1111/vco.12361
  • Peer Reviewed / Open Access
• [Journal Article] Bosutinib, an SRC inhibitor, induces caspase-independent cell death associated with permeabilization of lysosomal membranes in melanoma cells. (2017)
  • Author(s): Noguchi S, Shibutani S, Fukushima K, Mori T, Igase M, Mizuno T.
  • Journal Title: Vet Comp Oncol Volume: 印刷中 Issue: 1 Pages: 69-76
  • DOI: 10.1111/vco.12312
  • Peer Reviewed
• [Journal Article] Programmed Cell Death Ligand 1 Expression in Canine Cancer. (2016)
  • Author(s): Shosu K, Sakurai M, Inoue K, Nakagawa T, Sakai H, Morimoto M, Okuda M, Noguchi S, Mizuno T.
  • Journal Title: In Vivo Volume: 30 Pages: 195-204
  • Peer Reviewed
• [Journal Article] Oncolytic reovirus synergizes with chemotherapeutic agents to promote cell death in canine mammary gland tumor (2016)
  • Author(s): Igase M, Hwang CC, Kambayashi S, Kubo M, Coffey M, Miyama TS, Baba K, Okuda M, Noguchi S, Mizuno T
  • Journal Title: Can J Vet Res. Volume: 80 Pages: 21-31
  • Peer Reviewed
• [Presentation] Development of therapeutic antibody for canine cancers. (2018)
  • Author(s): Mizuno T.
  • Organizer: The 9th Joint Symposium of Veterinary Research in East Asia
  • Int'l Joint Research / Invited
• [Presentation] Pilot study of oncolytic reovirus therapy in dogs with spontaneouasly occurring tumors. (2017)
  • Author(s): Igase M, Hwang CC, Sakurai M, Shimokawa T, Haraguchi T, Tani K, Itamoto K, Nakaichi M, Nemoto Y, Shimokawa T, Okuda M, Noguchi S, Mizuno T.
  • Organizer: Asian Meeting of Animal Medicine Specialties 2017
  • Int'l Joint Research
• [Presentation] ATM kinaseの阻害は、犬の悪性黒色腫細胞株においてレオウイルスの細胞死を促進する (2017)
  • Author(s): 伊賀瀬雅也、野口俊助、水野拓也
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Inhibition of the ATM enhaned the reovirus-induced cell death in canine melanoma cells. (2017)
  • Author(s): Igase M, Mizuno T.
  • Organizer: The 5th Sapporo Summer Seminar for One Health
  • Int'l Joint Research
• [Presentation] ATM kinase阻害による犬メラノーマ細胞株に対する腫瘍溶解性ウイルスの細胞傷害増強効果の検討 (2017)
  • Author(s): 伊賀瀬雅也、野口俊助、根本有希、水野拓也
  • Organizer: 第160回日本獣医学会学術集会