Establishment of new immunotherapy targeting novel co-inhibitory molecule DC-HIL against canine malignant melanoma

• Project/Area Number: 15K18798
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• 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, 助教 (00722282)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 犬 / 悪性黒色腫 / 免疫抑制 / DC-HIL

Outline of Final Research Achievements

Our aim of this project is the establishment of new immunotherapy targeting novel co-inhibitory molecule DC-HIL against canine malignant melanoma. DC-HIL expressed by malignant melanoma cells acted in an inhibitory manner in the tumor immune reaction and showed that tumor growth was promoted. In a case of canine malignant melanoma, we found that DC-HIL in which tumor cells are expressed is involved in the immunosuppression of tumor-bearing individuals and that the prognosis may be poor. In addition, we revealed that anti-dog DC-HIL antibody can inhibit immunosuppressive function by DC-HIL expressed by canine malignant melanoma cells.

Research Products

• [Journal Article] Selective growth inhibition by suppression of F1Fo ATPase in canine malignant melanoma cell lines. (2017)
  • Author(s): Kuroki S, Kobayashi M, Tani H, Miyamoto R, Kurita S, Tamura K, Ono K, Washizu T, Bonkobara M.
  • Journal Title: J Vet Pharmacol Ther Volume: 40 Issue: 1 Pages: 101-104
  • DOI: 10.1111/jvp.12336
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular Characterization of the Cytidine Monophosphate-N-Acetylneuraminic Acid Hydroxylase (CMAH) Gene Associated with the Feline AB Blood Group System. (2016)
  • Author(s): Omi T, Nakazawa S, Udagawa C, Tada N, Ochiai K, Chong YH, Kato Y, Mitsui H, Gin A, Oda H, Azakami D, Tamura K, Sako T, Inagaki T, Sakamoto A, Tsutsui T, Bonkobara M, Tsuchida S, Ikemoto S.
  • Journal Title: PLoS One Volume: 11 Issue: 10 Pages: e0165000-e0165000
  • DOI: 10.1371/journal.pone.0165000
  • Peer Reviewed / Open Access
• [Journal Article] Molecular changes associated with the development of resistance to imatinib in an imatinib-sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation (2015)
  • Author(s): Kobayashi M, Kuroki S, Tanaka Y, Moriya Y, Kozutumi Y, Uehara Y, Ono K, Tamura K, Washizu T, Bonkobara M.
  • Journal Title: Eur J Haematol. Volume: In press Issue: 6 Pages: 524-31
  • DOI: 10.1111/ejh.12526
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 犬の骨髄由来抑制細胞と悪性腫瘍との関連 (2017)
  • Author(s): 田村恭一
  • Organizer: 第13回日本獣医内科学アカデミー学術大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2017-02-18
  • Invited
• [Presentation] 犬の骨髄由来抑制細胞と悪性腫瘍との関連 (2016)
  • Author(s): 田村恭一
  • Organizer: 日本獣医臨床病理学会2016年大会
  • Place of Presentation: 日本獣医生命科学大学（東京都武蔵野市）
  • Year and Date: 2016-05-29
  • Invited
• [Presentation] 担がん犬における末梢血中骨髄由来免疫抑制細胞の量的解析 (2016)
  • Author(s): 宮本拓弥、藤原万里子、山本華以、山下諒、田村恭一、盆子原誠
  • Organizer: 日本獣医臨床病理学会2016年大会
  • Place of Presentation: 日本獣医生命科学大学（東京都武蔵野市）
  • Year and Date: 2016-05-29
• [Presentation] Molecular changes associated with the development of resistance to Imatinib in an Imatinibe-sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation. (2015)
  • Author(s): M. Kobayashi, S. Kuroki, Y. Uehara, Y. Kozutsumi, Y. Tanaka, Y. Moriya, K. Tamura, T. Washizu, M. Bonkobara.
  • Organizer: American college of internal veterinary medicine forum.
  • Place of Presentation: 米国 インディアナポリス
  • Year and Date: 2015-06-07
  • Int'l Joint Research
• [Presentation] 伴侶動物における担がん個体の免疫抑制細胞 (2015)
  • Author(s): 田村恭一
  • Organizer: 日本獣医臨床病理学会
  • Place of Presentation: 日本獣医生命科学大学（東京都武蔵野市）
  • Year and Date: 2015-05-30
  • Invited
• [Presentation] 犬の肥満細胞腫のイマチニブ耐性化に関する臨床的および細胞生物学的解析 (2015)
  • Author(s): 守口昌悟、小林正人、佐野文郁、林麻央、池田紘子、今井貴昌、山下傑夫、小野憲一郎、田村恭一、盆子原誠、鷲巣月美
  • Organizer: 日本獣医臨床病理学会
  • Place of Presentation: 日本獣医生命科学大学（東京都武蔵野市）
  • Year and Date: 2015-05-30
• [Presentation] イマチニブ抵抗性を示したKIT exon 9変異(c.1523A>T)を有する肥満細胞腫の犬の一例 (2015)
  • Author(s): 林麻央、佐野文郁、守口昌悟、池田紘子、今井貴昌、小林正人、安田暁子、田村恭一、盆子原誠、鷲巣月美
  • Organizer: 日本獣医臨床病理学会
  • Place of Presentation: 日本獣医生命科学大学（東京都武蔵野市）
  • Year and Date: 2015-05-30
• [Book] 犬と猫の治療ガイド2015 私はこうしている (2015)
  • Author(s): 田村恭一
  • Total Pages: 6
  • Publisher: interzoo