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Combination immunotherapy of oncolytic virus and dendritic cells for bladder tumor

Research Project

Project/Area Number 16K10996
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionKyorin University (2018-2019)
The University of Tokyo (2016-2017)

Principal Investigator

Fukuahra Hiroshi  杏林大学, 医学部, 教授 (20292948)

Co-Investigator(Kenkyū-buntansha) 本間 之夫  東京大学, 医学部附属病院, 登録診療員 (40165626)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords膀胱癌 / ウイルス療法 / 遺伝子治療 / 樹状細胞 / iPS / iPS細胞 / 免疫療法 / 腫瘍学
Outline of Final Research Achievements

We investigated the efficacy of using a combination immunotherapy of dendritic cells and a newly-developed oncolytic virus: herpes simplex virus type 1 (HSV-1) expressing IL-12, a cytokine that enhances dendritic cell function, to suppress tumor growth in a subcutaneous mice model of bladder cancer. New oncolytic HSV-1 expressing IL-12 plus dendritic cells were more efficient than mono-therapy alone in reducing tumor volume, promoting CD8+ lymphocyte infiltration and increasing IFN-γ expression in the MB49 bladder cancer xenograft model. As a conclusion, combination therapy of dendritic cells with oncolytic HSV-1 expressing IL-12 is a promising option for bladder cancer treatment.

Academic Significance and Societal Importance of the Research Achievements

進行性膀胱癌はきわめて難治であり、革新的な治療法の開発が期待されている。今回、IL-12を発現したウイルスを用いてさらにウイルス療法の効果を増強すると同時に、ウイルス療法にて破壊された癌を樹状細胞に認識させて抗腫瘍免疫を誘導させる「抗癌ウイルス免疫療法」を行う点において独創的であり、学術的意義があると考えている。また、今回使用したウイルスの元のがん治療用ウイルスは既に脳腫瘍などで臨床試験が進行中であり、今回、腫瘍効果が確認されれば、臨床応用に向けてすぐに動き出せるというトランスレーショナルリサーチとしての社会的意義も有する。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (39 results)

All 2019 2018 2017 2016

All Journal Article (24 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 20 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 11 results)

  • [Journal Article] Oncolytic virus therapy in Japan: progress in clinical trials and future perspectives2019

    • Author(s)
      Satoru Taguchi, Hiroshi Fukuhara, Tomoki Todo
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 49 Issue: 3 Pages: 201-209

    • DOI

      10.1093/jjco/hyy170

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular Taxonomy of Interstitial Cystitis/Bladder Pain Syndrome Based on Whole Transcriptome Profiling by Next-Generation RNA Sequencing of Bladder Mucosal Biopsies2019

    • Author(s)
      Akiyama Yoshiyuki、Maeda Daichi、Katoh Hiroto、Morikawa Teppei、Niimi Aya、Nomiya Akira、Sato Yusuke、Kawai Taketo、Goto Akiteru、Fujimura Tetsuya、Fukuhara Hiroshi、Nakagawa Tohru、Igawa Yasuhiko、Ishikawa Shumpei、Fukayama Masashi、Kume Haruki、Homma Yukio
    • Journal Title

      Journal of Urology

      Volume: 印刷中 Issue: 2 Pages: 290-300

    • DOI

      10.1097/ju.0000000000000234

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of Mirabegron on Anxiety and Depression in Female Patients with Overactive Bladder.2019

    • Author(s)
      Kinjo M, Yamaguchi T, Tambo M, Okegawa T, Fukuhara H.
    • Journal Title

      Urol Int.

      Volume: 102(3) Issue: 3 Pages: 331-335

    • DOI

      10.1159/000497282

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extent of Hunner lesions: The relationships with symptom severity and clinical parameters in Hunner type interstitial cystitis patients2018

    • Author(s)
      Akiyama Yoshiyuki、Niimi Aya、Nomiya Akira、Yamada Yukio、Nakagawa Tohru、Fujimura Tetsuya、Fukuhara Hiroshi、Kume Haruki、Igawa Yasuhiko、Homma Yukio
    • Journal Title

      Neurourology and Urodynamics

      Volume: 37 Issue: 4 Pages: 1441

    • DOI

      10.1002/nau.23467

    • URL

      https://pure.teikyo.jp/en/publications/7662b3a1-f0d2-4623-994b-1b05e28030bf

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibitory effects of silodosin on the bladder mechanosensitive afferent activities and their relation with bladder myogenic contractions in male rats with bladder outlet obstruction2018

    • Author(s)
      Aizawa Naoki、Watanabe Daiji、Fukuhara Hiroshi、Fujimura Tetsuya、Kume Haruki、Homma Yukio、Igawa Yasuhiko
    • Journal Title

      Neurourology and Urodynamics

      Volume: 37 Issue: 6 Pages: 1897-1903

    • DOI

      10.1002/nau.23547

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nine primary malignant neoplasms-involving the esophagus, stomach, colon, rectum, prostate, and external ear canal-without microsatellite instability: a case report2018

    • Author(s)
      Arakawa Keiichi、Hata Keisuke、Yamamoto Yoko、Nishikawa Takeshi、Tanaka Toshiaki、Kiyomatsu Tomomichi、Kawai Kazushige、Nozawa Hiroaki、Yoshida Masafumi、Fukuhara Hiroshi、Fujishiro Mitsuhiro、Morikawa Teppei、Yamasoba Tatsuya、Koike Kazuhiko、Fukayama Masashi、Watanabe Toshiaki
    • Journal Title

      BMC Cancer

      Volume: 18 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s12885-017-3973-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aggressive cancer behavior of latent gleason pattern 5 in prostatectomy specimens2018

    • Author(s)
      FUJIMURA TETSUYA、FUKUHARA HIROSHI、YAMADA YUTA、TAGUCHI SATORU、SUGIHARA TORU、NIIMI AYA、NAKAMURA MASAKI、NAKAGAWA TOHRU、IGAWA YASUHIKO、HOMMA YUKIO、KUME HARUKI
    • Journal Title

      Anticancer Research

      Volume: 38 Issue: 11 Pages: 6529

    • DOI

      10.21873/anticanres.13018

    • URL

      https://pure.teikyo.jp/en/publications/10c21e2a-a3c6-497c-b63f-fcf9d6c4a258

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hospital-Volume Effects on Perioperative Outcomes in Peritoneal Dialysis Catheter Implantation: Analysis of 2,505 Cases2018

    • Author(s)
      Kinoshita Yoshitaka、Sugihara Toru、Yasunaga Hideo、Matsui Hiroki、Ishikawa Akira、Fujimura Tetsuya、Fukuhara Hiroshi、Ishibashi Yoshitaka、Fushimi Kiyohide、Homma Yukio
    • Journal Title

      Peritoneal Dialysis International

      Volume: 38 Issue: 6 Pages: 419-423

    • DOI

      10.3747/pdi.2017.00095

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of neutrophil-to-lymphocyte ratio in collecting duct carcinoma2018

    • Author(s)
      Taguchi Satoru、Fukuhara Hiroshi、Miyakawa Jimpei、Morikawa Teppei、Naito Akihiro、Kawai Taketo、Fujimura Tetsuya、Kume Haruki
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 48 Issue: 7 Pages: 692-694

    • DOI

      10.1093/jjco/hyy076

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of random bladder biopsy in primary T1 bladder cancer2018

    • Author(s)
      Otsuka Masafumi、Taguchi Satoru、Nakagawa Tohru、Morikawa Teppei、Maekawa Shigekatsu、Miyakawa Jimpei、Matsumoto Akihiko、Miyazaki Hideyo、Fujimura Tetsuya、Fukuhara Hiroshi、Kume Haruki、Igawa Yasuhiko、Homma Yukio
    • Journal Title

      Molecular and Clinical Oncology

      Volume: 8 Pages: 665-670

    • DOI

      10.3892/mco.2018.1587

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oncological and peri-surgical outcomes of radical prostatectomy for non-metastatic prostate cancer with prostate-specific antigen level of 50 ng/ml or greater2018

    • Author(s)
      Makino Katsuhiro、Nakagawa Tohru、Ito Eisaku、Kasahara Ichiro、Murata Takashi、Fujimura Tetsuya、Fukuhara Hiroshi、Homma Yukio
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 48 Issue: 5 Pages: 485

    • DOI

      10.1093/jjco/hyy044

    • URL

      https://pure.teikyo.jp/en/publications/877dbc00-6c08-4cc9-ad26-83619ab8fe3d

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preoperative chronic kidney disease is predictive of oncological outcome of radical cystectomy for bladder cancer.2018

    • Author(s)
      4.Matsumoto A, Nakagawa T, Kanatani A, Ikeda M, Kawai T, Miyakawa J, Taguchi, S, Naito A, Otsuka M, Nakanishi Y, Suzuki M, Koga F, Nagase Y, Kondo Y, Okaneya T, Tanaka Y, Miyazaki H, Fujimura T, Fukuhara H, Kume H, Igawa Y,Homma Y.
    • Journal Title

      World J Urol

      Volume: 36 Issue: 2 Pages: 249-256

    • DOI

      10.1007/s00345-017-2141-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predictors of Early Continence after Robot-assisted Radical Prostatectomy2017

    • Author(s)
      YAMADA Yuta、FUJIMURA Tetsuya、FUKUHARA Hiroshi、SUGIHARA Toru、NAKAGAWA Tohru、KUME Haruki、IGAWA Yasuhiko、HOMMA Yukio
    • Journal Title

      Low Urin Tract Symptoms

      Volume: - Issue: 3 Pages: 287-291

    • DOI

      10.1111/luts.12181

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diagnostic value of urinary CXCL10 as a biomarker for predicting Hunner type interstitial cystitis2017

    • Author(s)
      Niimi Aya、Igawa Yasuhiko、Aizawa Naoki、Honma Toshiki、Nomiya Akira、Akiyama Yoshiyuki、Kamei Jun、Fujimura Tetsuya、Fukuhara Hiroshi、Homma Yukio
    • Journal Title

      Neurourol Urodyn

      Volume: 37(3) Issue: 3 Pages: 1113-1119

    • DOI

      10.1002/nau.23431

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Overactive bladder is a negative predictor of achieving continence after robot-assisted radical prostatectomy2017

    • Author(s)
      Yamada Yuta、Fujimura Tetsuya、Fukuhara Hiroshi、Sugihara Toru、Miyazaki Hideyo、Nakagawa Tohru、Kume Haruki、Igawa Yasuhiko、Homma Yukio
    • Journal Title

      Int J Urol

      Volume: 24 Issue: 10 Pages: 749

    • DOI

      10.1111/iju.13411

    • URL

      https://localhost/en/publications/a630ce5f-2805-42b0-ad17-7c6613421804

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prevalence and characteristics of fecal antimicrobial-resistant Escherichia coli in a cohort of Japanese men undergoing prostate biopsy2017

    • Author(s)
      Kamei Jun、Yagihara Yuka、Kume Haruki、Horiuchi Takamasa、Sato Tomoaki、Nakagawa Tohru、Fujimura Tetsuya、Fukuhara Hiroshi、Moriya Kyoji、Homma Yukio
    • Journal Title

      Int J Urol

      Volume: 24 Issue: 4 Pages: 295

    • DOI

      10.1111/iju.13308

    • URL

      https://pure.teikyo.jp/en/publications/9c5548d9-725e-45ed-80c8-04c4bded8b4c

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Robot-assisted radical prostatectomy significantly reduced biochemical recurrence compared to retro pubic radical prostatectomy2017

    • Author(s)
      Fujimura Tetsuya、Fukuhara Hiroshi、Taguchi Satoru、Yamada Yuta、Sugihara Toru、Nakagawa Tohru、Niimi Aya、Kume Haruki、Igawa Yasuhiko、Homma Yukio
    • Journal Title

      BMC Cancer

      Volume: 17 Issue: 1 Pages: 454-454

    • DOI

      10.1186/s12885-017-3439-6

    • URL

      https://pure.teikyo.jp/en/publications/d7c05655-185e-47dd-b28b-53e6f6787d0e

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Accessibility to surgical robot technology and prostate-cancer patient behavior for prostatectomy2017

    • Author(s)
      Sugihara Toru、Yasunaga Hideo、Matsui Hiroki、Nagao Go、Ishikawa Akira、Fujimura Tetsuya、Fukuhara Hiroshi、Fushimi Kiyohide、Ohori Makoto、Homma Yukio
    • Journal Title

      Jpn J Clin Oncol

      Volume: 47 Issue: 7 Pages: 647-651

    • DOI

      10.1093/jjco/hyx052

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Incidence and risk factors of inguinal hernia after robot-assisted radical prostatectomy2017

    • Author(s)
      Taguchi S, Fukuhara H*, Homma Y, Todo T.
    • Journal Title

      Int J Urol

      Volume: 15 Issue: 1

    • DOI

      10.1186/s12957-017-1126-3

    • URL

      https://pure.teikyo.jp/en/publications/7992c224-6de2-4a75-aeef-60273174d07a

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oncolytic virus therapy: A new era of cancer treatment at dawn.2016

    • Author(s)
      Fukuhara H, Ino Y, Todo T.
    • Journal Title

      Cancer Sci

      Volume: 107 Issue: 5 Pages: 1373-1379

    • DOI

      10.1111/iju.13325

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【泌尿器科から発信する医療イノベーション】 遺伝子組換えウイルスを用いたがん治療開発2016

    • Author(s)
      福原 浩、田口 慧、本間之夫
    • Journal Title

      泌尿器外科

      Volume: 29 Pages: 351-354

    • Related Report
      2016 Research-status Report
  • [Journal Article] 【新薬認可で治療革命の幕開け がんのウイルス療法 がん細胞だけを破壊する組換えウイルスその作用機序と開発動向】 遺伝子組換え単純ヘルペスウイルスI型 G47Δを用いた日本発ウイルス療法薬開発の挑戦2016

    • Author(s)
      福原 浩、藤堂具紀
    • Journal Title

      実験医学

      Volume: 34 Pages: 8-12

    • Related Report
      2016 Research-status Report
  • [Journal Article] 【新前立腺癌学-最新の基礎研究と診断・治療-】 臨床応用を目指した基礎研究 新規治療開発 ヘルペスウイルスを用いたウイルス療法2016

    • Author(s)
      角谷成紀、福原 浩、本間之夫
    • Journal Title

      日本臨床

      Volume: 74増刊3 Pages: 244-247

    • Related Report
      2016 Research-status Report
  • [Journal Article] 【基礎研究から臨床への架け橋】遺伝子組換えヘルペスを用いたウイルス療法:臨床試験を中心に2016

    • Author(s)
      角谷成紀、福原 浩、本間之夫
    • Journal Title

      Prostate journal

      Volume: 3 Pages: 7-10

    • Related Report
      2016 Research-status Report
  • [Presentation] 前立腺癌に対するウイルス療法2019

    • Author(s)
      福原浩
    • Organizer
      2019中日先進医療と新薬研究サミット及び成果実業化大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Oncolytic virus therapy in Patients with Castration-Resistant Prostate Cancer2019

    • Author(s)
      福原浩
    • Organizer
      ARO協議会第7回学術集会 第5回台湾-日本ARO workshop
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 緩徐増殖性腫瘍に対するプロモータ制御型がん治療用ヘルペスウイルスの活用~後 腹膜脂肪肉腫での検討2019

    • Author(s)
      田口慧
    • Organizer
      第107回日本泌尿器科医会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 前立腺癌 ホルモン療法と手術、そしてウイルス療法2019

    • Author(s)
      福原 浩
    • Organizer
      第2回 UrologicalForum in城北
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 前立腺癌にはやはり手術とホルモン療法!2018

    • Author(s)
      福原 浩
    • Organizer
      第43回 神戸Urogenital Tumor Conference
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 前立腺癌にはやはり手術とホルモン療法!2018

    • Author(s)
      福原 浩
    • Organizer
      第19回 杏林イブニングセミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 前立腺癌には、手術とホルモン療法2018

    • Author(s)
      福原 浩
    • Organizer
      わかしゃち泌尿器科セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] がん治療:次の波はウイルス療法か2018

    • Author(s)
      福原 浩
    • Organizer
      第56回日本癌治療学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 前立腺癌にはやはり手術とホルモン療法!2018

    • Author(s)
      福原 浩
    • Organizer
      千葉泌尿器科集団会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] がん治療用ウイルスG47deltaを用いた去勢抵抗性前立腺癌に対するウイルス療法の臨床研究2017

    • Author(s)
      福原 浩
    • Organizer
      第105回日本泌尿器科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] A phase 1 study of an oncolytic HSV-1 G47delta in patients with castration resistant prostate cancer2017

    • Author(s)
      福原 浩
    • Organizer
      第23回日本遺伝子治療学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 何故、新規バイオマーカーが必要なのか?役に立つバイオマーカーは見つかるのか?2017

    • Author(s)
      福原 浩
    • Organizer
      日本泌尿器腫瘍学会 第3回学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] A phase 1 study of a third-generation oncolytic HSV-1 G47∆ in patients with castration resistant prostate cancer,2016

    • Author(s)
      Hiroshi Fukuhara, Yuta Takeshima, Yukio Homma, Yasushi Ino, Tomoki Todo
    • Organizer
      American Urological Association (AUA) 2016 Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 第三世代ヘルペスウイルスG47Δを用いたウイルス療法の去勢抵抗性前立腺癌に対する臨床研究2016

    • Author(s)
      福原 浩、竹島雄太、藤村哲也、宮嵜英世、中川 徹、久米春喜、本間之夫、稲生 靖、藤堂具紀
    • Organizer
      第104回日本泌尿器科学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Research-status Report
  • [Presentation] 前立腺癌に対する私見およびウイルス療法の臨床試験について2016

    • Author(s)
      福原 浩
    • Organizer
      山梨前立腺癌検診フォーラム
    • Place of Presentation
      甲府
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2022-01-27  

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