Development of combination therapy of cytokine signaling suppressor virus and anti-PD-L1 antibody

• Project/Area Number: 17K16907
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Nagoya University
• Principal Investigator: Ichinose Toru 名古屋大学, 医学系研究科, 研究員 (60778091)
• Research Collaborator: KASUYA hideki ; NAOE yoshinori ; MATSUMURA shigeru ; BUSTOS itzel ; EISSA ibrahim
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍溶解性ウイルス / 癌 / サイトカインシグナル / 免疫チェックポイント / 頭頸部がん

Outline of Final Research Achievements

The purpose of this study was to develop new treatments by combining oncolytic virus HF10 that was genetically modified to express the inhibitory regulator SOCS1 of the Jak / Stat pathway in the viral genome and the immune checkpoint inhibitor to improve treatment outcome for head and neck cancer. A foreign gene cassette vector was constructed, and we succeeded in creating HF10-SOCS1 into which the regulatory SOCS1 gene was integrated by homologous recombination with the HF10 genome. We examined the combined effect of HF10-SOCS1 and immune checkpoint inhibitors on bilateral flank tumors of mouse squamous cell carcinoma SCC7 cell line and showed a stronger antitumor effect than HF10 on both tumors.

Academic Significance and Societal Importance of the Research Achievements

本研究では、HF10-SOCS1 の感染と免疫チェックポイント阻害剤の投与により癌免疫抑制環境が改善され、癌抗原特異的T 細胞が腫瘍に強く浸潤し、体内のT細胞の機能も長く維持される事が期待される。本研究によって得られた結果はウイルス療法の新たな展開だけでなく、免疫細胞療法分野にも新しい知見を提供し、外科的切除のみでは治癒不可能な多くの癌患者さんの生命予後に寄与する可能性がある。

Research Products

• [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
• [Journal Article] A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer (2018)
  • Author(s): Hirooka Yoshiki、Kasuya Hideki、Ishikawa Takuya、Kawashima Hiroki、Ohno Eizaburo、Villalobos Itzel B.、Naoe Yoshinori、Ichinose Toru、Koyama Nobuto、Tanaka Maki、Kodera Yasuhiro、Goto Hidemi
  • Journal Title: BMC Cancer Volume: 18 Issue: 1 Pages: 596-596
  • DOI: 10.1186/s12885-018-4453-z
  • Peer Reviewed / Open Access
• [Journal Article] Curative effect of HF10 on liver and peritoneal metastasis mediated by host antitumor immunity (2017)
  • Author(s): Hotta Y, Kasuya H, Bustos I, Naoe Y, Ichinose T, Tanaka M, Kodera Y
  • Journal Title: Oncolytic Virotherapy Volume: 6 Pages: 31-38
  • DOI: 10.2147/ov.s127179
  • Peer Reviewed / Open Access
• [Presentation] The synergistic effect of the combination therapy of PD-L1 immune checkpoint inhibitor and oncolytic herpes simplex virus Canerpaturev(C-REV) (2018)
  • Author(s): Yoshinori Naoe, Nobuaki Mukoyama, Ibrahim Eissa, Toru Ichinose, Shigeru Matsumura, Itzel Bustos, Wu Zhiwen, Noriyuki Miyajima, Daishi Morimoto, Maki Tanaka, Yasushi Fujimoto, Michihiko Sone, Yasuhiro Kodera, Hideki Kasuya
  • Organizer: 第56回日本癌治療学会学術集会
• [Presentation] The synergistic effect of the combination therapy of PD-L1 immune checkpoint inhibitor and oncolytic herpes simplex virus HF10 (2018)
  • Author(s): Nobuaki Mukoyama, Ibrahim Eissa, Yoshinori Naoe, Toru Ichinose, Shigeru Matsumura, Itzel Bustos, Wu Zhiwen, Noriyuki Miyajima, Daishi Morimoto, Maki Tanaka, Yasushi Fujimoto, Michihiko Sone, Yasuhiro Kodera, Hideki Kasuya
  • Organizer: 第24回日本遺伝子細胞治療学会学術集会
• [Presentation] Combination therapy of oncolytic HSV HF10 and immune checkpoint inhibitor (2018)
  • Author(s): H Kasuya, Y Naoe, S Matsumura, I Bustos, T Ichinose, I Eissa, W Zhiwen, N Miyajima, D Morimoto, M Tanaka
  • Organizer: International Oncolytic Virus Conference 2018
  • Int'l Joint Research
• [Presentation] ヒト膵癌異種移植モデルにおけるnab-Paclitaxel（nab-PTX）と腫瘍溶解性単純ヘルペスウイルスHF10 との併用療法 (2017)
  • Author(s): 森本 大士, 直江 吉則, 一ノ瀬 亨, Bustos Itzel, 神田 光郎, 丹羽 由紀子, 岩田 直樹, 林 真路, 小林 大介, 田中 千恵, 山田 豪, 中 山 吾郎, 杉本 博行, 小池 聖彦, 藤原 道隆, 藤井 努, 田中 舞紀, 粕谷 英樹, 小寺 泰弘
  • Organizer: 第117 回日本外科学会定期学術集会
• [Presentation] ヒト大腸がんモデルにおけるセツキシマブとの併用による腫瘍溶解性ウイルスHF10 の抗腫瘍効果 (2017)
  • Author(s): 呉 智聞, 一ノ瀬 亨, 駱 晨虹, 直江 吉則, イッツェル・ブストス・ビジャロボス, 山田 豪, 藤井 努, 杉本 博行, 森本 大士, 向山 宣 昭, 小寺 泰弘, 田中 舞紀, 粕谷 英樹
  • Organizer: 第117 回日本外科学会定期学術集会
• [Presentation] HF10 ウイルス療法におけるin situ vaccination効果についての検討 (2017)
  • Author(s): 粕谷 英樹, 直江 吉則, Bustos Itzel, 一ノ瀬 亨, 森本 大士, 向山 宣昭, 呉 智聞, 藤井 努, 小寺 泰弘, 田中 舞紀
  • Organizer: 第117 回日本外科学会定期学術集会
• [Presentation] Combination therapy of oncolytic herpes virus and anti-angiogenesis agent (bevacizumab) against human gastric cancer xenograft (2017)
  • Author(s): H. Kasuya, G. Tan, C. Luo, T. Ichinose, I. Bustos, Y. Naoe
  • Organizer: EACR-AACR-SIC Special Conference 2017
  • Int'l Joint Research
• [Presentation] Systemic therapeutic potential of oncolytic herpes simplex virus HF10 adsorbed on antigen-specific lymphocytes (2017)
  • Author(s): Ichinose T, Naoe Y, Nassr E. I. R, Luo C, Villalobos I. B, Zhiwen W, Mukoyama N, Miyajima N, Morimoto D, Yamada S, Fujii T, Sugimoto H, Tanaka M, Kodera Y, Kasuya H.
  • Organizer: 第23回日本遺伝子細胞治療学会学術集会
• [Presentation] Combination therapy of PD-L1 immune checkpoint inhibitor and oncolytic herpes simplex virus HF10 (2017)
  • Author(s): Mukoyama N, Naoe Y, Ichinose T, Nassr E. I. R, Luo C, Villalobos I. B, Zhiwen W, Miyajima N, Morimoto D, Tanaka M, Fujimoto Y, Sone M, Kodera Y, Kasuya H.
  • Organizer: 第23回日本遺伝子細胞治療学会学術集会
• [Book] 遺伝子医学MOOK 31号 がん免疫療法 - What's now and what's next? 第2章の4の3) 腫瘍溶解性ウイルス HF10による再発乳がん多発結節症例, 切除不能進行膵がん症例に対する臨床研究 (2017)
  • Author(s): 粕谷 英樹, 直江 吉則, 一ノ瀬 亨, 廣岡 芳樹, 後藤 秀実, 田中 舞紀
  • Total Pages: 294
  • Publisher: (株)メディカル ドゥ
• [Remarks] 名古屋大学大学院医学系研究科 癌免疫治療研究室
  • URL: https://www.med.nagoya-u.ac.jp/intlexch/cancerimmuno/www/index.html