Development of a novel less invasive therapeutic intervention for early-stage colorectal cancers using cancer-specific targeting agent

• Project/Area Number: 24790700
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Okayama University
• Principal Investigator: KISHIMOTO HIROYUKI 岡山大学, 大学病院, 助教 (50613155)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 消化器内視鏡学 / 大腸癌 / アデノウイルスベクター / 内視鏡治療

Outline of Final Research Achievements

Endoscopic submucosal dissection (ESD) is one of the treatment options for early colorectal cancer. However, cases diagnosed with submucosal (SM) invasion after ESD need surgery. We hypothesized that in SM invasive cases, local tumor resection with a telomerase-dependent tumor killing adenoviral agent (OBP-301) dosing might inhibit LN metastasis. In this study, we assessed whether resection of primary tumor in a similar manner to ESD with prior OBP-301 injection into the peritumoral SM space could purge LN metastasis. Our study demonstrated that OBP-301 could completely eradicate regional LNs metastasis in the SM invasive rectal tumor mouse model with spontaneous LN metastasis by the injection of OBP-301 into the peritumoral submucosal space mimicking the ESD procedures. Virus-mediated biological ablation with the standard ESD technique provides a potential alternative to prophylactic surgery for SM invasive colorectal cancer patients.

Research Products

• [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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of a clinically-precise mouse model of rectal cancer. (2013)
  • Author(s): Kishimoto H, Momiyama M, Aki R, Kimura H, Suetsugu A, Bouvet M, Fujiwara T, Hoffman RM
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e79453-e79453
  • DOI: 10.1371/journal.pone.0079453
  • Peer Reviewed
• [Presentation] テロメラーゼ依存性増殖型アデノウイルス製剤を用いた早期大腸癌の微小リンパ節転移制御 (2014)
  • Author(s): 菊地覚次、岸本浩行、田澤 大、黒田新士、西崎正彦、香川俊輔、浦田泰生、ロバートホフマン、藤原俊義
  • Organizer: 第73回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Molecular surgery using a novel biological agent, OBP-301, for lymph node micrometastasis in human colorectal cancer. (2014)
  • Author(s): Kikuchi S, Kishimoto H, et al
  • Organizer: 2014 ASCO Annual Meeting
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] Combination strategy of endoscopic resection and telomerase-targeting oncolytic virus (OBP-301) for eradicating lymph node metastasis of submucosal invasive colorectal cancer (2014)
  • Author(s): Hori N, Kikuchi S, Kishimoto H, et al
  • Organizer: AACR 2014
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] テロメラーゼ依存性増殖型アデノウイルス製剤を用いた早期大腸癌に対する低侵襲治療の開発 (2014)
  • Author(s): 菊地覚次、岸本浩行、田澤 大、橋本悠里、宇野 太、西崎正彦、香川俊輔、浦田泰生、ロバートホフマン、藤原俊義
  • Organizer: 第114回日本外科学会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] Novel strategy for eradicating lymph node metastasis of early-stage colorectal cancers using telomerase-dependent replicating adenoviral agent (2013)
  • Author(s): Kikuchi S, Kishimoto H, et al
  • Organizer: 第19回日本遺伝子治療学会
  • Place of Presentation: 岡山
• [Presentation] テロメラーゼ依存性増殖型アデノウイルス製剤を用いた早期大腸癌の低侵襲治療の開発 (2013)
  • Author(s): 菊地覚次、岸本浩行、田澤 大、橋本悠里、宇野 太、西崎正彦、香川俊輔、浦田泰生、ロバートホフマン、藤原俊義
  • Organizer: 第68回日本消化器外科学会総会
  • Place of Presentation: 宮崎
• [Presentation] Novel strategy for eradicating lymph node metastasis of early-stage colorectal cancers (2013)
  • Author(s): Kikuchi S, Kishimoto H, et al
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] がん選択的生物製剤を用いた早期大腸癌の低侵襲治療の開発 (2013)
  • Author(s): 菊地覚次、岸本浩行、田澤 大、宇野 太、西崎正彦、香川俊輔、浦田泰生、ロバートホフマン、藤原俊義
  • Organizer: 第51回日本癌治療学会
  • Place of Presentation: 京都
• [Presentation] Novel strategy for eradicating lymph node metastasis of early-stage colorectal cancers using telomerase-dependent replicating adenoviral agent. (2013)
  • Author(s): Kikuchi S, Kishimoto H, et al
  • Organizer: AACR 2013
  • Place of Presentation: Washington, DC, USA
• [Presentation] Less invasive therapeutic intervention for early colorectal cancers using telomerase-dependent replicating adenovirus. (2013)
  • Author(s): Kikuchi S, Kishimoto H, et al
  • Organizer: 第113回日本外科学会総会
  • Place of Presentation: 福岡
• [Presentation] Novel less invasive therapeutic intervention for early-stage colorectal cancers using telomerase-dependent replicating adenoviral agent. (2012)
  • Author(s): Kikuchi S, Kishimoto H, et al
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
• [Presentation] Novel strategy for eradicating lymph node metastasis of early-stage colorectal cancers using Telomelysin. (2012)
  • Author(s): Kikuchi S, Kishimoto H, et al
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌