Systemic virotherapy using oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes

• Project/Area Number: 25293275
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Nagoya University
• Principal Investigator: KASUYA Hideki 名古屋大学, 医学(系)研究科(研究院), 准教授 (00402636)
• Co-Investigator(Kenkyū-buntansha): KODERA Yasuhiro 名古屋大学, 医学系研究科, 教授 (10345879) ; UCHIDA Hiroaki 東京大学, 医科学研究所, 講師 (20401250) ; YAMADA Suguru 名古屋大学, 医学部附属病院, 病院講師 (30467287) ; SHIKU Hiroshi 三重大学, 医学系研究科, 産学連携講座教員 (80154194) ; NOMOTO Shuji 名古屋大学, 医学部附属病院, 病院講師 (40300967)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: HF10 / 腫瘍溶解性ウイルス / 悪性黒色腫 / ヒッチハイクメソッド / リンパ球療法 / Drug delivery

Outline of Final Research Achievements

In this study, we investigated the possibility of systemic administration of HF10 adsorbed on the tumor antigen-specific lymphocytes. We administered adsorbed HF10 to the tail vein of mice with subcutaneous tumor expressed ovalbumin antigen and analyzed the efficacy of this treatment. HF10 absorbed on ovalbumin antigen-specific T cells showed significant antitumor effect more than control group. Our results suggest that HF10 adsorbed on tumor antigen-specific lymphocytes could be delivered systemically without interference of host immune response, and it have significant potential in treatment of the disseminated tumors. We acquired precious basic data for clinical trial.

Research Products

• [Journal Article] Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft (2015)
  • Author(s): Gewen Tan, Hideki Kasuya, Tevfik Tolga Sahin, Kazuo Yamamura, Zhiwen Wu, Yusuke Koide, Yoshihiro Hotta, Toshio Shikano, Suguru Yamada, Akiyuki Kanzaki, Tsutomu Fujii, Hiroyuki Sugimoto, Shuji Nomoto, Yoko Nishikawa, Maki Tanaka, Naoko Tsurumaru, Toshie Kuwahara, Saori Fukuda, Toru Ichinose, Yasuhiro Kodera, et al.
  • Journal Title: International Journal of Cancer Volume: 136 Pages: 1718-1730
  • DOI: 10.1002/ijc.29163
  • Peer Reviewed / Open Access
• [Journal Article] Phase I Dose-escalation Clinical Trial of HF10 Oncolytic Herpes Virus in 17 Japanese Patients with Advanced Cancer (2014)
  • Author(s): Hideki Kasuya, Yasuhiro Kodera, Akimasa Nakao, Kazuo Yamamura, Tan Gewen, Wu Zhiwen, Yoshihiro Hotta, Suguru Yamada, Tsutomu Fujii, Saori Fukuda, Naoko Tsurumaru, Toshie Kuwahara, Toyone Kikumori, Yusuke Koide, Yasushi Fujimoto, Tsutomu Nakashima, Yoshiki Hirooka, Hiroshi Shiku, Maki Tanaka, et al.
  • Journal Title: Hepato-Gastroenterology Volume: 61 Pages: 599-605
  • Peer Reviewed
• [Journal Article] Combination treatment of human pancreatic cancer xenograft models with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib and oncolytic herpes simplex virus HF10. (2014)
  • Author(s): Yamamura K, Kasuya H
  • Journal Title: Ann Surg Oncol. Volume: 21(2) Pages: 691-698
  • DOI: 10.1245/s10434-013-3329-3
  • Peer Reviewed
• [Journal Article] Phase I Dose-escalation Clinical Trial of HF10 Oncolytic Herpes Virus in 17 Japanese Patients with Advanced Cancer (2014)
  • Author(s): Kasuya H, Kodera Y
  • Journal Title: Hepatogastroenterology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Concurrent chemotherapy inhibits herpes simplex virus-1 replication and oncolysis (2013)
  • Author(s): Kulu Y, Kasuya H
  • Journal Title: Cancer Gene Ther. Volume: 20(2) Pages: 133-140
  • DOI: 10.1038/cgt.2012.97
  • Peer Reviewed
• [Presentation] Clinical Trial Using Oncolytic Virus HF10 in Japan (2016)
  • Author(s): 粕谷 英樹
  • Organizer: Pusan National University Gene and Cell Therapy Research Centerの開所式
  • Place of Presentation: Pusan National University Yangsan Campus （大韓民国 梁山(Yangsan)市）
  • Year and Date: 2016-01-07
  • Int'l Joint Research
• [Presentation] Systemic virotherapy using oncolytic herpes simplex virus adsorbed onto antigenspecific lymphocytes (2015)
  • Author(s): Toru Ichinose，Akiyuki Kanzaki，Luo Chenhong，Yoshihiro Hotta，Koide Yusuke， Wu Zhiwen， Saori Fukuda，Toshie Kuwahara，Suguru Yamada，Tsutomu Fujii，Hiroyuki Sugimoto，Maki Tanaka，Yasuhiro Kodera，Hideki Kasuya
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場 （福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] Anti-tumor immunity with locally administered HF10 effects to the liver and peritoneal metastasis in mouse models (2015)
  • Author(s): Hideki Kasuya, Yoshihiro Hota, Chenhong Luo, Toru Ichinose Zhiwen Wu, Noriyuki Miyazima, Nobuaki Mukouyama, Yusuke Koide , Maki Tanaka , Yasuhiro Kodera
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場 （愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Combination therapy against human pancreatic cancer with oncolytic herpes virus hrR3 and monoclonal antibody bevacizumab (2015)
  • Author(s): Zhiwen Wu, Toru Ichinose, Chenhong Luo, Gewen Tan, Tevfik T. Sahin, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Yoko Nishikawa, Usuke Koide, Saori Fukuda, Yasuhiro Kodera, Hideki Kasuya
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場 （愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Tumor targeting strategy of oncolytic herpes simplex virus using hitchhiking on antigen-specific lymphocytes (2015)
  • Author(s): Toru Ichinose, Akiyuki Kanzaki, Chenhong Luo, Yoshihiro Hotta, Yusuke Koide, Wu Zhiwen, Saori Fukuda, Toshie Kuwahara, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Maki Tanaka, Yasuhiro Kodera, Hideki Kasuya
  • Organizer: 第21回日本遺伝子治療学会学術集会
  • Place of Presentation: 大阪国際会議場 （大阪府大阪市）
  • Year and Date: 2015-07-24
• [Presentation] Enhancing anti-tumor immune response of HF10 virotherapy through HSV amplicon carrying cancer therapeutic gene (2015)
  • Author(s): Luo C., Shibata K., Goshima F., Wu Z., Hotta Y., Ichinose T., Koide Y., Tanaka M., Kodera Y., Kasuya H.
  • Organizer: 第21回日本遺伝子治療学会学術集会
  • Place of Presentation: 大阪国際会議場 （大阪府大阪市）
  • Year and Date: 2015-07-24
• [Presentation] COMBINATION THERAPY AGAINST HUMAN COLORECTAL CANCER WITH THE EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITOR CETUXIMAB AND ONCOLYTIC HERPES SIMPLEX VIRUS HF10 (2015)
  • Author(s): Wu Z., Ichinose T., Luo C., Tan G., Yamada S., Fujii T., Sugimoto H., Nishikawa Y., Hotta Y., Koide U., Fukuda S., Kuwahara T., Kodera Y., Tanaka M., Kasuya H
  • Organizer: 第21回日本遺伝子治療学会学術集会
  • Place of Presentation: 大阪国際会議場 （大阪府大阪市）
  • Year and Date: 2015-07-24
• [Presentation] Combination treatment of human head and neck cancer xenograft models with cetuximab and oncolytic herpes simplex virus HF10 (2015)
  • Author(s): Koide Y., Zhiwen W., Hotta Y., Ichinose T., Luo C., Tanaka M., Fujimoto Y., Kodera Y., Kasuya H.
  • Organizer: 第21回日本遺伝子治療学会学術集会
  • Place of Presentation: 大阪国際会議場 （大阪府大阪市）
  • Year and Date: 2015-07-24
• [Presentation] EXPERIENCE OF TRANSLATIONAL RESEARCH USING HERPES ONCOLYTIC VIRUS HF10 IN NAGOYA UNIVERSITY HOSPITAL (2015)
  • Author(s): 粕谷 英樹、山村 和生、、堀田 佳宏、藤井 努、中尾 昭公、西山 幸廣、田中 舞紀、小寺 泰弘
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: アクトシティ浜松，オークラアクトシティホテル浜松，ホテルクラウンパレス浜松 （静岡県浜松市）
  • Year and Date: 2015-07-15
• [Presentation] 膵癌モデルに対する腫瘍溶解性ヘルペスウイルス HF10 とエルロチニブとの併用療法 (2015)
  • Author(s): 粕谷英樹、山村和生、堀田佳宏、Wu Zhewen, 一ノ瀬亨、小出悠介、桑原寿江、山田豪、藤井努、田中舞紀、小寺泰弘
  • Organizer: 第46回日本膵臓学会大会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-19
• [Presentation] Potential Therapeutic Effectivity for Combination of HF10 with Erlotinib and Gemcitabine (2015)
  • Author(s): Hideki Kasuya, Kazuo Yamamura, Yoshihiro Hotta, Tan Gewen, Wu Zhiwen, Toru Ichinose, Toshie Kuwahara, Yusuke Koide, Maki Tanaka, Yasuhiro Kodera
  • Organizer: the 9th International Conferenthece on Oncolytic Virus Therapeutics
  • Place of Presentation: Boston Park Plaza Hotel （アメリカ合衆国 マサチューセッツ州 ボストン）
  • Year and Date: 2015-06-13
  • Int'l Joint Research
• [Presentation] 腫瘍溶解性ウイルスによる抗腫瘍細胞免疫の誘導効果の検討 (2015)
  • Author(s): 一ノ瀬亨、粕谷英樹、堀田佳宏、神崎章之、城田高、Wu Zhiwen、桑原寿江、山田豪、藤井努、杉本博行、小寺泰弘
  • Organizer: 第36回癌免疫外科研究会
  • Place of Presentation: 奄美観光ホテル （鹿児島県奄美市）
  • Year and Date: 2015-05-14
• [Presentation] Translational study using herpes oncolytic virus HF10 with Erlotinib and Gemcitabine (2014)
  • Author(s): Kasuya H., Yamamura K., Hotta Y., Tan G., Wu Z., Fukuda S., Kuwahara T., Hirooka Y., Goto H., Koide Y., Tanaka M, Kodera Y.
  • Organizer: 第20回日本遺伝子治療学会学術集会
  • Place of Presentation: 東京慈恵会医科大学 (東京都港区)
  • Year and Date: 2014-08-06 – 2014-08-08
• [Presentation] COMBINATION THERAPY OF ONCOLYTIC HERPES SIMPLEX VIRUS HF10 AND BEVACIZUMAB AGAINST EXPERIMENTAL MODEL OF HUMAN BREAST CARCINOMA (2014)
  • Author(s): Gewen Tan, Hideki Kasuya, Tevfik Tolga Sahin, Kazuo Yamamura, Toshio Shikano, Suguru Yamada, Akiyuki Kanzaki, Tsutomu Fujii, Hiroyuki Sugimoto, Shuji Nomoto, Yoko Nishikawa, Maki Tanaka, Naoko Tsurumaru, Shin Takeda, Akimasa Nakao, Yasuhiro Kodera
  • Organizer: 第20回日本遺伝子治療学会学術集会
  • Place of Presentation: 東京慈恵会医科大学 (東京都港区)
  • Year and Date: 2014-08-06 – 2014-08-08
• [Presentation] A PROMISING THERAPY AGAINST HUMAN GASTRIC CANCER XENOGRAFT WITH THE COMBINATION OF BEVACIZUMAB AND ONCOLYTIC VIRUS hrR3 (2014)
  • Author(s): Zhiwen Wu, Gewen Tan, Hideki Kasuya, Tevfik T Sahin, Toshio Shikano, Suguru Yamada, Akiyuki Kanzaki, Kazuo Yamamura, Tsutomu Fujii, Hiroyuki Sugimoto, Shuji Nomoto, Yoko Nishikawa, Yoshihiro Hotta, Usuke Koide, Saori Fukuda, Naoko Tsurumaru, Toshie Kuwahara, Shin Takeda，Akimasa Nakao and Yasuhiro Kodera
  • Organizer: 第20回日本遺伝子治療学会学術集会
  • Place of Presentation: 東京慈恵会医科大学 (東京都港区)
  • Year and Date: 2014-08-06 – 2014-08-08
• [Presentation] ANTI-TUMOR ACTIVITY OF ONCOLYTIC HERPES SIMPLEX VIRUS HF10 IN COMBINATION WITH THE EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITOR ERLOTINIB IN HUMAN PANCREATIC CANCERS (2014)
  • Author(s): Yusuke Koide, Kazuo Yamamura, Hideki Kasuya, Wu Zhiwen, Gewen Tan, Yoshihiro Hotta, Mitsuro Kanda, Saori Fukuda, Toshie Kuwahara, Suguru Yamada, Goro Nakayama, Tsutomu Fujii, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara, Maki Tanaka, Yasushi Fujimoto, Yasuhiro Kodera
  • Organizer: 第20回日本遺伝子治療学会学術集会
  • Place of Presentation: 東京慈恵会医科大学 (東京都港区)
  • Year and Date: 2014-08-06 – 2014-08-08
• [Presentation] HF10の皮下腫瘍への局所投与における肝転移および腹膜播種への宿主の腫瘍免疫を介した波及治療効果の検討 (2014)
  • Author(s): 堀田佳宏 粕谷英樹 山村和生 神田光朗 山田豪 藤井努 杉本博行 野本周嗣 小寺泰弘
  • Organizer: 第35回癌免疫外科研究会
  • Place of Presentation: シェラトン都ホテル大阪 （大阪府大阪市）
  • Year and Date: 2014-05-22 – 2014-05-23
• [Presentation] POSSIBILITY OF COMBINATION THERAPY USING HERPES ONCOLYTIC VIRUS HF10 WITH ERLOTINIB AND GEMCITABINE AS PRECLINICAL DATA FOR CLINICAL TRIAL (2014)
  • Author(s): Hideki Kasuya, Kazuo Yamamura, Tan Gewen, Tevfik T Sahin, Yoshiki Hirooka, Hidemi Goto, Yasuhiro Kodera, Maki Tanaka
  • Organizer: 8th International Conference on Oncolytic Virus Therapeutics
  • Place of Presentation: Oxford University （イギリス オックスフォード）
  • Year and Date: 2014-04-10 – 2014-04-13
• [Presentation] Combination therapy of oncolytic herpes virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft (2014)
  • Author(s): Gewen Tan, Hideki Kasuya, Tevfik Tolga Sahin, Toshio Shikano, Suguru Yamada, Akiyuki Kanzaki, Kazuo Yamamura, Tsutomu Fujii, Hiro-yuki Sugimoto, Shuji Nomoto, Yoko Nishikawa, Maki Tanaka, Naoko Tsurumaru, Shin Takeda, Akimasa Nakao, Yasuhiro Kodera
  • Organizer: AACR Annual Meeting 2014 （American Association for Cancer Research）
  • Place of Presentation: San Diego Convention Center (San Diego, California, USA）
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Combination therapy of oncolytic herpes virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft (2014)
  • Author(s): Tan G, Kasuya H
  • Organizer: The 105th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: San Diego, USA
• [Presentation] POSSIBILITY OF COMBINATION THERAPY USING HERPES ONCOLYTIC VIRUS HF10 WITH ERLOTINIB AND GEMCITABINE AS PRECLINICAL DATA FOR CLINICAL TRIAL (2014)
  • Author(s): Kasuya H
  • Organizer: the 8th International Conference on Oncolytic Virus Therapeutics
  • Place of Presentation: Oxford, UK
• [Presentation] HF10の皮下腫瘍への局所投与における肝転移および腹膜播種への宿主の腫瘍免疫を介した波及治療効果の検討 (2014)
  • Author(s): 堀田佳宏, 粕谷英樹
  • Organizer: 第35回癌免疫外科研究会
  • Place of Presentation: シェラトン都ホテル大阪（大阪市）
• [Book] 次世代のがん治療薬・診断のための研究開発 (2016)
  • Author(s): 粕谷 英樹、松田 正、関根勇一、鍛代悠一、織谷健司、仲 一仁、武藤 倫弘、石川 秀樹、藤井 元、宮本 真吾、若林 敬二、高橋 智、鈴木 周吾、佐藤 慎哉、内木 綾、久野 壽也、藤村 隆、尾山勝信、宮下知治、太田哲生、他
  • Total Pages: 400
  • Publisher: （株）技術情報協会
• [Book] 分子細胞治療フロンティア2015 腫瘍溶解性ウイルスHF10: Combination Therapyの有用性 (2014)
  • Author(s): 粕谷英樹、小寺泰弘、山田豪、後藤秀実、廣岡芳樹、川嶋啓揮、田中舞紀
  • Total Pages: 236
  • Publisher: 飯田橋パピルス
• [Book] 「分子細胞治療フロンティア2015」第３章 腫瘍溶解性ウイルスHF10: Combination Therapyの有用性 (2014)
  • Author(s): 粕谷英樹、小寺泰弘
  • Publisher: 飯田橋パピルス
• [Remarks] 腫瘍溶解性ウイルスは「抗がん剤」と成り得るか?
  • URL: http://www.med.nagoya-u.ac.jp/surgery2/scientific/study/virus/aboutvirus/