Novel treatment for neuroblastoma by using live-attenuated poliovirus

• Project/Area Number: 15K09650
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: TOYODA HIDEMI 三重大学, 医学部附属病院, 講師 (60525327)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 神経芽腫 / ポリオウイルス / oncolytic virotherapy

Outline of Final Research Achievements

We have demonstrated that neuroblastoma (NB) subcutaneously implanted in immuno-competent mice is eliminated by intratumoral administration of poliovirus (PV). Our results also suggested that the in vivo destruction of NB cells by virotherapy lead to a robust antitumor immune response. Since we used CD155-transfected NB for experiments, CD155 might be a target for antitumor immune response. Although NB can grow in naïve mice, no tumor growth was observed in mice cured of NB that were reinnoculated with NB cells.
Splenocytes harvested from NB-bearing mice treated with PV exhibited higher lytic activity against NB cells than did those from splenocytes derived from naïve mice. In vitro T-cell depletion experiments indicated that CD8+ T cells were essential for the cytotoxic antitumor activity of splenocytes.

Research Products

• [Journal Article] The effects of inherited NUDT15 polymorphisms on thiopurine active metabolites in Japanese children with acute lymphoblastic leukemia. (2018)
  • Author(s): Moriyama T, Nishii R, Lin TN, Kihira K, Toyoda H, Jacob N, Kato M, Koh K, Inaba H, Manabe A, Schmiegelow K, Yang JJ, Hori H.
  • Journal Title: Pharmacogenet Genomics Volume: 27 Pages: 236-239
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo (2018)
  • Author(s): Xu Dong-Qing、Toyoda Hidemi、Yuan Xiao-Jun、Qi Lei、Chelakkot Vipin Shankar、Morimoto Mari、Hanaki Ryo、Kihira Kentarou、Hori Hiroki、Komada Yoshihiro、Hirayama Masahiro
  • Journal Title: Exp Cell Res. Volume: 365 Issue: 2 Pages: 177-184
  • DOI: 10.1016/j.yexcr.2018.02.032
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High-dose Cepharanthin for pediatric chronic immune thrombocytopenia in Japan. (2017)
  • Author(s): Yamazaki T, Shibuya A, Ishii S, Miura N, Ohtake A, Sasaki N, Araki R, Ota Y, Fujiwara M, Miyajima Y, Uetake K, Hamahata K, Kato K, Kawakami K, Toyoda H, Moriguchi N, Okada M, Nishi M, Ogata Y, Takimoto T, Ohga S, Ohta S, Amemiya S.
  • Journal Title: Pediatr Int. Volume: 59 Issue: 3 Pages: 303-308
  • DOI: 10.1111/ped.13151
  • Peer Reviewed
• [Journal Article] Ewing Sarcoma of the Bone With EWS/FLI1 Translocation After Successful Treatment of Primary Osteosarcoma. (2017)
  • Author(s): Yodoya N, Iwamoto S, Matsumine A, Azuma E, Toyoda H, Miura Y, Nakatani K, Imai H, Hirayama M, Komada Y.
  • Journal Title: J Pediatr Hematol Oncol. Volume: 39 Pages: 6-9
  • Peer Reviewed
• [Journal Article] Disease Recurrence After Early Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome With Complement C3 I1157T Mutation. (2016)
  • Author(s): Toyoda, H., Wada, H., Miyata, T., Amano, K., Kihira, K., Iwamoto, S., Hirayama, M., Komada, Y.
  • Journal Title: J Pediatr Hematol Oncol Volume: 38 Issue: 3 Pages: e137-e139
  • DOI: 10.1097/mph.0000000000000505
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PDK1-mTOR signaling pathway inhibitors reduce cell proliferation in MK2206 resistant neuroblastoma cells. (2015)
  • Author(s): Qi L, Toyoda H, Xu DQ, Zhou Y, Sakurai N, Amano K, Kihira K, Hori H, Azuma E, Komada Y
  • Journal Title: Cancer Cell International Volume: 15 Issue: 1 Pages: 1-14
  • DOI: 10.1186/s12935-015-0261-6
  • Peer Reviewed / Int'l Joint Research