Analysis of antitumor immunity induced by vaccinia virus with in vivo imaging

• Project/Area Number: 25462254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kyoto University
• Principal Investigator: Arakawa Yoshiki 京都大学, 医学(系)研究科(研究院), 助教 (20378649)
• Co-Investigator(Kenkyū-buntansha): Dean Thumkeo 京都大学, 医学研究科, 助教 (40372594)
• Co-Investigator(Renkei-kenkyūsha): Matsuda Michiyuki 京都大学, 医学研究科, 教授 (10199812)
• Research Collaborator: Murata Daiki ; Fujimoto Ko-ichi ; Yokogawa Ryuta ; Terada Yukinori ; Fukui Nobuyuki ; Liu Bin
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 悪性脳腫瘍 / ワクシニアウイルス / 生体イメージング / 腫瘍免疫 / 免疫誘導 / ウイルス治療 / 悪性グリオーマ

Outline of Final Research Achievements

The aim of the project is to analyze oncolytic bioresponse induced by vaccinia virus, and to develop the new oncolytic therapy. Our previous results indicate that the antitumor immunity activated by vaccinia virus is effective for malignant brain tumors. In brain tumor models, the induction of antitumor immune competent cells was identified by immunohistochemical staining and flow cytometry, although it was not sufficient for long-term tumor control. As Flt3L is known to be a strong stimulator of antitumor immune system, Flt3L-expressing vaccinia virus has been developed. The in vivo analyzing system of antitumor immunity has been prepared to evaluate efficacy of Flt3L-expressing vaccinia virus. The status of antitumor immunity in medulloblastoma was analyzed. We confirmed that high PD-L1 expression and low CD8+ lymphocyte infiltration was associated with worse survival in patients with medulloblastoma.

Research Products

• [Journal Article] Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury (2016)
  • Author(s): 1.Hideo Chihara, Yasushi Takagi, Kazunari Nishino, Kazumichi Yoshida, Yoshiki Arakawa, Takayuki Kikuchi, Yohei Takenobu, Susumu Miyamoto
  • Journal Title: Neurologia medico-chirurgica Volume: 56 Issue: 1 Pages: 33-37
  • DOI: 10.2176/nmc.oa.2015-0178
  • NAID: 130005119820
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High mobility group A1 expression shows negative correlation with recurrence time in patients with glioblastoma multiforme. (2015)
  • Author(s): 4.Bin Liu, Bo Pang, Huajie Liu, Yoshiki Arakawa, Rui Zhang, Bin Feng, Peng Zhong, Daiki Murata, Haitao Fan, Tao Xin, Guangyu Zhao, Wei Liu, Hua Guo, Liming Luan, Shangchen Xu, Susumu Miyamoto, Qi Pang.
  • Journal Title: Pathology - Research and Practice Volume: 211 Issue: 8 Pages: 596-600
  • DOI: 10.1016/j.prp.2015.05.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] rimary central nervous system lymphoma: is absence of intratumoral hemorrhage a characteristic finding on MRI? (2015)
  • Author(s): 5.Akihiko Sakata, Tomohisa Okada, Akira Yamamoto, Mitsunori Kanagaki, Yasutaka Fushimi, Toshiki Dodo, Yoshiki Arakawa, Jun C Takahashi, Susumu Miyamoto, Kaori Togashi.
  • Journal Title: Radiology and Oncology Volume: 49 Issue: 2 Pages: 128-134
  • DOI: 10.1515/raon-2015-0007
  • Peer Reviewed / Open Access
• [Journal Article] Grading glial tumors with amide proton transfer MR imaging: different analytical approaches. (2015)
  • Author(s): Sakata, A., T. Okada, A. Yamamoto, M. Kanagaki, Y. Fushimi, T.Okada, T. Dodo, Y. Arakawa, B. Schmitt, S. Miyamoto, K.
  • Journal Title: J Neurooncol Volume: 122 Issue: 2 Pages: 339-48
  • DOI: 10.1007/s11060-014-1715-8
  • Peer Reviewed
• [Journal Article] Efficacy of salvage stereotactic radiotherapy for recurrent glioma: impact of tumor morphology and method of target delineation on local control. (2013)
  • Author(s): Kengo Ogura, Takashi Mizowaki, Yoshiki Arakawa, Katsuyuki Sakanaka, Susumu Miyamoto, Masahiro Hiraoka..
  • Journal Title: Molecular and Clinical Oncology Volume: 2(6): Issue: 6 Pages: 942-949
  • DOI: 10.1002/cam4.154
  • Peer Reviewed
• [Journal Article] Retrospective Analysis of Bevacizumab in Combination With Ifosfamide, Carboplatin, and Etoposide in Patients With Second Recurrence of Glioblastoma (2013)
  • Author(s): oshiki Arakawa, Takashi Mizowaki, Daiki Murata, Koichi Fujimoto, Takayuki Kikuchi, Takeharu Kunieda, Jun C. Takahashi, Yasushi Takagi, Susumu Miyamoto.
  • Journal Title: Neurologia medico-chirurgica Volume: 53 Issue: 11 Pages: 779-785
  • DOI: 10.2176/nmc.oa2013-0211
  • NAID: 10031196789
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Journal Article] Dysembryoplastic neuroepithelial tumor with rapid recurrence of pilocytic astrocytoma component. (2013)
  • Author(s): Takeuchi Y, Arakawa Y, Mikami Y, Matsumoto R, Miyamoto S.
  • Journal Title: Brain Tumor Pathol Volume: 31 Issue: 2 Pages: 144-8
  • DOI: 10.1007/s10014-013-0155-z
  • Peer Reviewed
• [Journal Article] Initial and cumulative recurrence patterns of glioblastoma after temozolomide-based chemoradiotherapy and salvage treatment: a retrospective cohort study in a single institution. (2013)
  • Author(s): K Ogura, T Mizowaki, Y Arakawa, M Ogura, K Sakanaka, S Miyamoto2 and M Hiraoka.
  • Journal Title: Radiation Oncology Volume: 8:97 Issue: 1 Pages: 1-9
  • DOI: 10.1186/1748-717x-8-97
  • NAID: 120005323035
  • Peer Reviewed
• [Journal Article] Organizing intracerebral hematoma mimicking a recurrent brain tumor on FDG-PET. (2013)
  • Author(s): Satoshi Nakajima, Tomohisa Okada, Yoshiki Arakawa, Yoshiki Mikami, Kaori Togashi
  • Journal Title: Clinical Nuclear Medicine, Volume: 38(11) Issue: 11 Pages: e411-e413
  • DOI: 10.1097/rlu.0b013e31827085ce
  • Peer Reviewed
• [Presentation] 膠芽腫初回再発に対する放射線療法併用BICE療法 (2015)
  • Author(s): 荒川芳輝、峰晴陽平、丹治正大、青木友和、上羽哲也、北条雅人、岩崎孝一、高橋淳B、國枝武治、高木康志、宮本享
  • Organizer: 第33回日本脳腫瘍学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-12-06
• [Presentation] Retrospective review of glioblastoma patients treated with bevacizumab-containing and non-bevacizumab-containing regimens in a single institution (2015)
  • Author(s): Yoshiki Arakawa, Takashi Mizowaki, Masahiro Tanji, Yohei Mineharu, Kengo Ogura, Megumi Uto, Takeharu Kunieda, Yasushi Takagi, Susumu Miyamoto
  • Organizer: The 20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
  • Place of Presentation: San Antonio, Texas
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] Endoscopic port surgeryの適応と限界 (2015)
  • Author(s): 荒川芳輝 姜裕 丹治正大 峰晴陽平 國枝武治 高木康志 宮本享
  • Organizer: 日本脳神経外科学会第74回学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2015-10-14
• [Presentation] Bevacizumab, ifosfamide, carboplatin, and etoposide (BICE) concomitant with radiotherapy in patients with first recurrence of glioblastoma after temozolomide treatment. (2015)
  • Author(s): Yoshiki Arakawa, Takashi Mizowaki, Yohei Mineharu, Masaharu Tanji, Kengo Ogura, Megumi Uto, Yasushi Takagi, Susumu Miyamoto
  • Organizer: the 12th Meeting of the Asian Society for Neuro-Oncology
  • Place of Presentation: Manila, Philippines
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] 中間型松果体実質腫瘍におけるソマトスタチン受容体発現の検討 (2015)
  • Author(s): 2015年5月29日（金）・30日（土）
  • Organizer: 第33回日本脳腫瘍病理学会学術集会
  • Place of Presentation: 高松
  • Year and Date: 2015-05-29
• [Presentation] 脳室近傍腫瘍に対する内視鏡単独手術の適応と限界 (2013)
  • Author(s): 荒川芳輝
  • Organizer: 第18回日本脳腫瘍の外科学会
  • Place of Presentation: 大津
• [Presentation] 脳室・脳室近傍腫瘍に対する内視鏡単独腫瘍摘出術 (2013)
  • Author(s): 荒川芳輝
  • Organizer: 第20回日本神経内視鏡学会
  • Place of Presentation: 山梨
• [Presentation] 脳室・脳室近傍腫瘍に対する内視鏡単独腫瘍摘出術 (2013)
  • Author(s): 荒川芳輝
  • Organizer: 日本脳神経外科学会・第72回学術総会
  • Place of Presentation: 横浜
• [Presentation] 悪性グリオーマに対するウイルス療法に伴う腫瘍免疫機構の解析 (2013)
  • Author(s): 村田大樹、荒川芳輝、藤本浩一、山口真、平田英周、宮本 享
  • Organizer: 第31回日本脳腫瘍学会学術集会
  • Place of Presentation: 宮崎
• [Presentation] 再々発膠芽腫に対するbevacizumab併用ICE療法の治療経験と多施設共同試験による検証の提案 (2013)
  • Author(s): 荒川芳輝、青木友和、上羽哲也、北条雅人、岩崎孝一、丹治正大、國枝武治、高橋淳B、高橋淳C、高木康志、宮本享
  • Organizer: 第31回日本脳腫瘍学会学術集会
  • Place of Presentation: 宮崎