Oncolytic virus targeting tumor associated mesenchymal stem cells

• Project/Area Number: 18H02691
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagoya University
• Principal Investigator: Matsumura Shigeru 名古屋大学, 医学系研究科, 特任講師 (60523511)
• Co-Investigator(Kenkyū-buntansha): 粕谷 英樹 名古屋大学, 医学系研究科, 教授 (00402636) ; 直江 吉則 名古屋大学, 医学系研究科, 特任准教授 (50392048) ; 一ノ瀬 亨 名古屋大学, 医学系研究科, 研究員 (60778091)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 腫瘍溶解性ウイルス / 癌免疫

Outline of Final Research Achievements

One of the mechanisms for immune suppression in pancreatic tumors is the recruitment of mesenchymal stem cells (MSC), which turn into tumor-associated fibroblasts. C-REV, our oncolytic virus, has been shown to dramatically change the tumor microenvironment. Here, we examined whether C-REV has the ability to kill MSC in the tumor tissue. A naturally mutated attenuated HSV1, C-REV cannot replicate inside the healthy normal cells. However, we found that C-REV can infect and replicate in the MSC. Furthermore, C-REV treatment on the MSC-injected pancreatic tumors showed decreased numbers of MSC in the mouse model.

Academic Significance and Societal Importance of the Research Achievements

本研究で派生的に検証し報告したSTING経路と腫瘍溶解性ウイルスの知見は、新規治療法の提案につながった。2’3’-cGAMPは天然のSTINGアゴニストであるが、様々なSTING アゴニストが世界中で開発競争を繰り広げている。腫瘍溶解性ウイルスとの併用療法は報告されておらず、今後臨床研究されていく可能性がある。

Research Products

• [Journal Article] C-REV Retains High Infectivity Regardless of the Expression Levels of cGAS and STING in Cultured Pancreatic Cancer Cells (2021)
  • Author(s): Daishi Morimoto, Shigeru Matsumura, Itzel Bustos-Villalobos, Patricia Angela Sibal, Toru Ichinose, Yoshinori Naoe, Ibrahim Ragab Eissa, ohamed Abdelmoneim, Nobuaki Mukoyama, Noriyuki Miyajima, Maki Tanaka, Yasuhiro Kodera and Hideki Kasuya
  • Journal Title: Cells Volume: 10 Issue: 6 Pages: 1-16
  • DOI: 10.3390/cells10061502
  • Peer Reviewed / Open Access
• [Journal Article] Oncolytic herpes simplex virus HF10 (canerpaturev, C-REV) promotes accumulation of CD8+PD-1- tumor-infiltrating T cells in PD-L1 enriched tumor microenvironment. (2021)
  • Author(s): Eissa I.R., Mukoyama N., Abdelmoneim, M., Naoe, Y., Matsumura, S., Bustos-Villalobos I., Ichinose T., Miyajima N., Morimoto D., Tanaka M., Fujimoto, Y., Kodera Y., Kasuya H.
  • Journal Title: Int. J. Cancer Volume: 1 Issue: 1 Pages: 1-14
  • DOI: 10.1002/ijc.33550
  • Peer Reviewed
• [Journal Article] The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers (2018)
  • Author(s): Eissa Ibrahim、Bustos-Villalobos Itzel、Ichinose Toru、Matsumura Shigeru、Naoe Yoshinori、Miyajima Noriyuki、Morimoto Daishi、Mukoyama Nobuaki、Zhiwen Wu、Tanaka Maki、Hasegawa Hitoki、Sumigama Seiji、Aleksic Branko、Kodera Yasuhiro、Kasuya Hideki
  • Journal Title: Cancers Volume: 10 Issue: 10 Pages: 356-356
  • DOI: 10.3390/cancers10100356
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 大腸癌モデルにおけるセツキシマブとC-REVとの併用治療効果について (2019)
  • Author(s): Shigeru Matsumura, Zhiwen Wu, Toru Ichinose, Yoshinori Naoe, Itzel Bustos Villalobos, Ibrahim Ragab Eissa, Suguru Yamada, Yasuhiro Kodera, Maki Tanaka, and Hideki Kasuya
  • Organizer: 日本癌学会
• [Presentation] Combination of cetuximab and oncolytic virus canepaturev synergistically inhibits human colorectal cancer growth (2019)
  • Author(s): Shigeru Matsumura, Zhiwen Wu, Toru Ichinose, Yoshinori Naoe, Itzel Bustos Villalobos, Ibrahim Ragab Eissa, Suguru Yamada, Yasuhiro Kodera, Maki Tanaka, and Hideki Kasuya
  • Organizer: 癌免疫学会
• [Presentation] Combination therapy of Cetuximab and CANERPATUREV suppresses human colorectal cancer growth (2019)
  • Author(s): Shigeru Matsumura, Zhiwen Wu, Toru Ichinose, Yoshinori Naoe, Itzel Bustos Villalobos, Ibrahim Ragab Eissa, Suguru Yamada, Yasuhiro Kodera, Maki Tanaka, and Hideki Kasuya
  • Organizer: 日本遺伝子細胞治療学会
• [Presentation] STING is dispensable for low susceptibility to C-REV (HF10) in pancreatic cancer cell lines (2018)
  • Author(s): Matsumura S, Morimoto D, Naoe Y, Ichinose T, Eissa IR, Tanaka M, Kodera Y, Kasuya H
  • Organizer: 日本癌学会
• [Presentation] STING is dispensable for low susceptibility to C-REV (HF10) in pancreatic cancer cell lines (2018)
  • Author(s): Matsumura S, Morimoto D, Naoe Y, Ichinose T, Eissa IR, Tanaka M, Kodera Y, Kasuya H
  • Organizer: 4th Annual Oncolytic virotherapy summit