Photoimmunotherapy for gastrointestinal cancer

• Project/Area Number: 25462021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: Tanabe Shunsuke 岡山大学, 大学病院, 助教 (20534770)
• Co-Investigator(Kenkyū-buntansha): KAGAWA Shunsuke 岡山大学, 大学病院, 准教授 (00362971) ; OYAMA Takanori 岡山大学, 大学病院, 助教 (10380164)
• Co-Investigator(Renkei-kenkyūsha): FUJIWARA Toshiyoshi 岡山大学, 大学院医歯薬学総合研究科, 教授 (00304303) ; TAZAWA Hiroshi 岡山大学, 大学病院, 助教 (90415513)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 光免疫療法 / HER2 / 腹膜播種 / アデノウイルス / 胃癌 / 近赤外線光線免疫療法 / 消化器癌 / 近赤外光線免疫療法

Outline of Final Research Achievements

The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of new treatments for gastric cancer.We hypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumab-based photoimmunotherapy (PIT) might provide excellent and selective antitumor effects for peritoneal dissemination of gastric cancer. Adenovirus/HER2-ECD(Ad/HER2-ECD) efficiently transduced HER2-ECD into HER2-negative gastric cancer cells. Trastuzumab-mediated PIT induced selective cell death of HER2-ECD-transduced tumor cells, even in heterogeneous gastric cancer cells.Anti-HER2 PIT integrated with adenoviral HER2-ECD gene transfer was applied in mice bearing peritoneal dissemination of HER2-negative gastric cancer. Intraperitoneal administration of Ad/HER2-ECD and Tra-IR700 with PIT inhibited peritoneal metastasis and prolonged the survival of mice. Molecular-targeted PIT integrated with gene transfer technology is a promising strategy.

Research Products

• [Int'l Joint Research] 国立がん研究所(米国)
• [Journal Article] Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment. (2018)
  • Author(s): Harada T, Yatabe Y, Takeshita M, Koga T, et al
  • Journal Title: Anticancer Res Volume: 17 Pages: 1114-1114
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Trastuzumab-based photoimmunotherapy integrated with viral HER2 transduction inhibits peritoneally disseminated HER2-negative cancer. (2016)
  • 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 Pages: 402-411
  • DOI: 10.1158/1535-7163.mct-15-0644
  • Peer Reviewed / Int'l Joint Research / 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: Mol Ther Volume: 23 Pages: 501-509
  • DOI: 10.1038/mt.2014.244
  • NAID: 120005537574
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Viral transduction of HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2 negative breast cancer cells (2015)
  • Author(s): Shimoyama K, Kagawa S, Ishida M, Watanabe S, Noma K, Takehara K, Tazawa H, Hashimoto Y, Tanabe S, Matsuoka J, Kobayashi H, Fujiwara T
  • Journal Title: Breast Cancer Res Treat Volume: 149 Pages: 597-605
  • DOI: 10.1007/s10549-015-3265-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular diagnosis and therapy for occult peritoneal metastasis in gastric cancer patients (2014)
  • Author(s): Kagawa S, Shigeyasu K, Ishida M, Watanabe M, Tazawa H, Nagasaka T, Shirakawa Y, Fujiwara T
  • Journal Title: World Journal of Gastroenterology Volume: 20 Pages: 17796-17803
  • DOI: 10.3748/wjg.v20.i47.17796
  • Peer Reviewed
• [Journal Article] A novel synergistic effect of iron depletion on antiangiogenic cancer therapy. (2013)
  • Author(s): Tazawa H, Kagawa S, Fujiwara T
  • Journal Title: Expert Opinion on Biological Therapy Volume: 13 Pages: 1569-1583
  • DOI: 10.1517/14712598.2013.845662
  • Peer Reviewed
• [Journal Article] Successfully treated pneumatosis cystoides intestinalis with pneumoperitoneum onset in a patient administered α-glucosidase inhibitor. (2013)
  • Author(s): Tanabe S, Shirakawa Y, Takehara Y, Maeda N, Katsube R, Ohara T, Sakurama K, Noma K, Fujiwara T.
  • Journal Title: Acta Med Okayama Volume: 67 Pages: 123-128
  • NAID: 120005232504
  • Peer Reviewed
• [Presentation] 標的陰性癌に対するPhotoimmunotherapy．抗原修飾による抗原陽転化と不均一性の克服． (2016)
  • Author(s): 香川 俊輔， 石田 道拡， 下山 京子， 竹原 清人， 野間 和広， 田辺 俊介， 渡邉 めぐみ， 田澤 大， 小林 久隆， 藤原 俊義
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: 徳島県徳島市
  • Year and Date: 2016-07-14
• [Presentation] HER2抗原で修飾された癌細胞に対するTrastuzumabを用いた近赤外線光線免疫療法の効果 (2014)
  • Author(s): 石田道拡, 香川俊輔, 下山京子, 竹原清人, 野間和広, 田澤 大, 黒田新士, 岸本浩行, 田邊俊介, 小林久隆, 藤原俊義
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2014-09-25
• [Presentation] ウイルスを用いたHER２陰性胃癌の強制的HER2標識化とTrastuzumabによる分子標的光免疫療法 (2014)
  • Author(s): 香川俊輔, 石田道拡, 田澤 大, 下山京子, 竹原清人, 野間和広, 渡辺めぐみ, 田辺俊介, 小林久隆, 藤原俊義
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 2014-07-16 – 2014-07-18
• [Presentation] Novel combination therapy of adenoviral gene transfer of HER2-extracellular domain and trastuzumab-based photoimmunotherapy for HER2 negative cancer cells (2014)
  • Author(s): Ishida M, Kagawa S, Shimoyama K, Takehara K, Noma K, Tanabe S, Tazawa H, Matsuoka J, Kobayashi H, Fujiwara T
  • Organizer: 2014 Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: 米国 サンディエゴ
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] "HER2遺伝子導入技術を用いたHER2陰性癌細胞に対する分子標的 光免疫療法" (2013)
  • Author(s): 石田道拡，香川俊輔，下山京子，竹原清人，野間和広，田澤 大，黒田新士，岸本浩行，田邊俊介，松岡順治，小林久隆，藤原俊義
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 東京都
• [Presentation] Virally tagging of HER2 extracellular domain sensitizes her2-negative gastric cancer cells to Trastuzumab-based photoimmunotherapy. (2013)
  • Author(s): Kagawa S, Shimoyama K, Tazawa H, Hashimoto Y, Takehara K, Kuroda S, Kishimoto H, Nishizaki M, Kobayashi H, Fujiwara T
  • Organizer: the 10th International Gastric Cancer Congress
  • Place of Presentation: ヴェローナ、イタリア
• [Remarks] 岡山大学 プレスリリース
  • URL: http://www.okayama-u.ac.jp/tp/release/release_id375.html