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"Cell-in-cell" activity-based tumor-specific delivery of biologics

Research Project

Project/Area Number 25293283
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionOkayama University

Principal Investigator

FUJIWARA Toshiyoshi  岡山大学, 医歯(薬)学総合研究科, 教授 (00304303)

Co-Investigator(Kenkyū-buntansha) KAGAWA Shunsuke  岡山大学, 大学病院, 准教授 (00362971)
SHIRAKAWA Yasuhiro  岡山大学, 大学院医歯薬学総合研究科, 准教授 (60379774)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords癌 / 遺伝子 / 細胞・組織 / 医療・福祉 / トランスレーショナルリサーチ / トランスレーショナルリサーチ
Outline of Final Research Achievements

"Cell-in-cell" denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion. HOZOT cells were successfully loaded via human CD46 antigen with an attenuated adenovirus containing the fiber protein of adenovirus serotype 35 (OBP-401/F35), in which the telomerase promoter regulates viral replication. OBP-401/F35–loaded HOZOT cells were efficiently internalized into human cancer cells and exhibited tumor-specific killing by release of viruses, even in the presence of anti-viral neutralizing antibodies. Moreover, intraperitoneal administration of HOZOT cells loaded with OBP-401/F35 significantly suppressed peritoneally disseminated tumor growth in mice.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (17 results)

All 2016 2015 2014 2013 2012

All Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Open Access: 3 results,  Acknowledgement Compliant: 5 results) Presentation (2 results)

  • [Journal Article] Targeted photodynamic virotherapy armed with a genetically encoded photosensitizer.2016

    • Author(s)
      Takehara K, Kagawa S, Fujiwara T, et al.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 15 Issue: 1 Pages: 199-208

    • DOI

      10.1158/1535-7163.mct-15-0344

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Trastuzumab-Based Photoimmunotherapy Integrated with Viral HER2 Transduction Inhibits Peritoneally Disseminated HER2-Negative Cancer2016

    • Author(s)
      Ishida M, Kagawa S, Shimoyama K, Takehara K, Noma K, Tanabe S, Shirakawa Y, Tazawa H, Kobayashi H, Fujiwara T
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 15 Issue: 3 Pages: 402-411

    • DOI

      10.1158/1535-7163.mct-15-0644

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Experimental curative fluorescence-guided surgery of highly-invasive glioblastoma multiforme selectively labeled with a killer-reporter adenovirus2015

    • Author(s)
      Yano S, Miwa S, Kishimoto H, Toneri M, Hiroshima Y, Yamamoto M, Bouvet M, Urata Y, Tazawa H, Kagawa S, Fujiwara T, Hoffman RM
    • Journal Title

      Mol Ther

      Volume: 23 Issue: 7 Pages: 1182-1188

    • DOI

      10.1038/mt.2015.63

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery.2015

    • Author(s)
      Yano S, Hiroshima Y, Maawy A, Kishimoto H, Suetsugu A, Miwa S, Toneri M, Yamamoto M, Katz MH, Fleming JB, Urata Y, Tazawa H, Kagawa S, Bouvet M, Fujiwara T, Hoffman RM.
    • Journal Title

      Cancer Gene Ther

      Volume: 22 Issue: 7 Pages: 344-50

    • DOI

      10.1038/cgt.2015.26

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer.2015

    • Author(s)
      Shigeyasu K, Nagasaka T, Mori Y, Yokomichi N, Kawai T, Fuji T, Kimura K, Umeda Y, Kagawa S, Goel A, Fujiwara T
    • Journal Title

      PLoS One

      Volume: 10 Issue: 6 Pages: e0130409-e0130409

    • DOI

      10.1371/journal.pone.0130409

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.2015

    • Author(s)
      Kikuchi S, Kishimoto H, Tazawa H, Hashimoto Y, Kuroda S, Nishizaki M, Nagasaka T, Shirakawa Y, Kagawa S, Urata Y, Hoffman RM, Fujiwara T.
    • Journal Title

      Mol Ther.

      Volume: 23(3) Issue: 4 Pages: 501-509

    • DOI

      10.1136/gutjnl-2014-306957

    • NAID

      120005537574

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.2015

    • Author(s)
      Kikuchi S, et al.
    • Journal Title

      Molecular Therapy

      Volume: 23 Issue: 3 Pages: 501-509

    • DOI

      10.1038/mt.2014.244

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Establishment of a non-invasive semi-quantitative bioluminescent imaging method for monitoring of an orthotopic esophageal cancer mouse model.2014

    • Author(s)
      Kuroda S, et al.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 12 Pages: e114562-e114562

    • DOI

      10.1371/journal.pone.0114562

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity.2014

    • Author(s)
      Yano S, et al.
    • Journal Title

      Oncotarget

      Volume: 5 Pages: 8729-8736

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatial-temporal FUCCI imaging of each cell in a tumor demonstrates locational dependence of cell cycle dynamics and chemoresponsiveness.2014

    • Author(s)
      Yano S, et al.
    • Journal Title

      Cell Cycle

      Volume: 13 Issue: 13 Pages: 2110-2119

    • DOI

      10.4161/cc.29156

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells.2013

    • Author(s)
      Hasei, J.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 12 Issue: 3 Pages: 314-325

    • DOI

      10.1158/1535-7163.mct-12-0869

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel synergistic effect of iron depletion on antiangiogenic cancer therapy.2013

    • Author(s)
      Ohara T, Noma K, Urano S, Watanabe S, Nishitani S, Tomono Y, Kimura F, Kagawa S, Shirakawa Y, Fujiwara T
    • Journal Title

      International Journal of Cancer

      Volume: 132 Issue: 11 Pages: 2705-2713

    • DOI

      10.1002/ijc.27943

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination.2013

    • Author(s)
      Shigeyasu, K.
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 71 Issue: 4 Pages: 937-943

    • DOI

      10.1007/s00280-013-2086-0

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent cancer stem-like cells into S/G2/M-phases.2013

    • Author(s)
      Yano S, Tazawa H, Hashimoto Y, Shirakawa Y, Kuroda S, Nishizaki M, Kishimoto H, Uno F, Nagasaka T, Urata Y, Kagawa S, Hoffman RM, Fujiwara T
    • Journal Title

      Clin Cancer Res

      Volume: 19 Issue: 23 Pages: 6495-6505

    • DOI

      10.1158/1078-0432.ccr-13-0742

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus2012

    • Author(s)
      Sasaki, T.
    • Journal Title

      Gene Therapy

      Volume: (Epub ahead of print) Issue: 1 Pages: 112-118

    • DOI

      10.1038/gt.2011.213

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 胃癌における蛍光発現ウイルスによる腹腔洗浄液診断:生物学的悪性度指標としての可能性.2013

    • Author(s)
      香川俊輔
    • Organizer
      第113回日本外科学会定期学術集会(シンポジウム)
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] テロメラーゼ活性を指標とする血中遊離癌細胞の高感度検出法の開発と遺伝子解析技術への応用.2013

    • Author(s)
      重安邦俊
    • Organizer
      第113回日本外科学会定期学術集会(ワークショップ)
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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