Enhanced antitumor efficacy of telomerase-selective oncolytic adenobiral agent OBP-301 with chemotherapy in osteosarcoma.

• Project/Area Number: 24890132
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Okayama University
• Principal Investigator: SASAKI TSUYOSHI 岡山大学, 医学部, 客員研究員 (90594812)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: テロメラーゼ / ウイルス療法 / 骨肉腫

Research Abstract

We investigated the chemosensitizing effect of a telomerase-specific replication-competent oncolytic adenovirus, OBP-301, in human osteosarcoma cells. OBP-301 infection enhanced the cytotoxic effect of chemotherapy and increased chemotherapy-mediated apoptosis through downregulation of Mcl-1 expression. Combination therapy significantly suppressed tumor growth in a subcutaneous xenograft model. These results suggest that combination therapy provides a novel therapeutic strategy for human osteosarcomas.

Research Products

• [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
  • Peer Reviewed
• [Journal Article] A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus (2012)
  • Author(s): Sasaki, T.
  • Journal Title: Gene Therapy Volume: (Epub ahead of print) Issue: 1 Pages: 112-118
  • DOI: 10.1038/gt.2011.213
  • Peer Reviewed
• [Journal Article] Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis (2012)
  • Author(s): Tazawa, H.
  • Journal Title: International Journal of Cancer Volume: (Epub ahead of print) Issue: 12 Pages: 2939-2950
  • DOI: 10.1002/ijc.27589
  • Peer Reviewed
• [Journal Article] Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells. (2012)
  • Author(s): Yoshida, R.
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 61 Issue: 11 Pages: 1905-1916
  • DOI: 10.1007/s00262-012-1249-x
  • Peer Reviewed
• [Presentation] Enhanced Chemosensitivity of Osteosarcoma Cells by Oncolytic Adenovirus-mediated Mcl-1 Downregulation (2014)
  • Author(s): Osaki S
  • Organizer: 60th Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: New Orleans. USA
• [Presentation] Enhanced Chemosensitivity of Osteosarcoma Cells by Oncolytic Adenovirus-mediated Mcl-1 Downregulation. (2014)
  • Author(s): 尾﨑 修平
  • Organizer: 60th Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: New Orleans, USA
• [Presentation] 骨・軟部肉腫細胞に対するテロメラーゼ特異的制限増殖型アデノウイルス療法 (2013)
  • Author(s): 国定俊之
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 骨肉腫に対する腫瘍融解アデノウイルスの抗がん剤感受性亢進作用 (2013)
  • Author(s): 尾﨑修平
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Oncolytic adenovirus-armed p53 induces apoptosis significantly through upregulating miR-93 and 106b in human osteosarcoma cells (2013)
  • Author(s): Hasei J
  • Organizer: 104th Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Washington DC. USA
• [Presentation] Chemosensitizing Effect of Telomerase-specific Oncolytic Adenovirus for Human Osteosarcomas via Induction of Apoptosis and Autophagy (2013)
  • Author(s): Osaki S
  • Organizer: 59th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: San Antonio, USA
• [Presentation] Oncolytic adenovirus-armed p53 induces apoptosis significantly through upregulating miR-93 and 106b in human osteosarcoma cells. (2013)
  • Author(s): 長谷井 嬢
  • Organizer: 104th Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Washington DC, USA
• [Presentation] Chemosensitizing Effect of Telomerase-specific Oncolytic Adenovirus for Human Osteosarcomas via Induction of Apoptosis and Autophagy (2013)
  • Author(s): 尾崎 修平
  • Organizer: Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: San Antonio, USA
• [Presentation] Oncolytic adenovirus-mediated p53 gene transfer induces antitumor effect in human osteosarcoma cells (2012)
  • Author(s): Hasei J
  • Organizer: 9th Asia Pacific Musculoskeletal Tumour Society Meeting
  • Place of Presentation: Kuala Lumpur, Malaysia
• [Presentation] 骨肉腫に対するテロメラーゼ依存性腫瘍融解ウイルス製剤と化学療法の併用療法 (2012)
  • Author(s): 尾﨑修平
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 骨肉腫に対するテロメラーゼ依存性腫瘍融解ウイルス製剤と化学療法の併用療法 (2012)
  • Author(s): 尾崎 修平
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Oncolytic adenovirus-mediated p53 gene transfer induces antitumor effect in human osteosarcoma cells (2012)
  • Author(s): 長谷井 嬢
  • Organizer: 9th Asia Pacific Musculoskeletal Tumour Society Meeting
  • Place of Presentation: Kuala Lumpur, Malaysia