Development of molecular-specific cancer theranostics utilizing near-infrared light and monoclonal antibody

• Project/Area Number: 26710010
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Mitsunaga Makoto 東京慈恵会医科大学, 医学部, 講師 (40433990)
• Research Collaborator: ITO KIMIHIRO 東京慈恵会医科大学, 医学部, 助教 (60794336) ; NISHIMURA TAKASHI 東京慈恵会医科大学, 大学院生
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: がん / 分子イメージング / 近赤外光 / 抗体療法 / 癌 / 分子標的薬

Outline of Final Research Achievements

Photoimmunotherapy (PIT) is a recently developed molecular-targeted cancer theranostics based on conjugating a near-infrared photoactivatable fluorescence probe to a monoclonal antibody targeting cancer cell surface molecules. In this project, we have developed several methods to enhance therapeutic outcomes of PIT. (1) PIT in combination with chemotherapy (2) PIT utilizing two monoclonal antibodies recognizing different epitopes of cancer antigen. (3) PIT utilizing photoactivatable bifunctional antibody-drug conjugates.

Research Products

• [Journal Article] Near-Infrared Photochemoimmunotherapy by Photoactivatable Bifunctional Antibody－Drug Conjugates Targeting Human Epidermal Growth Factor Receptor 2 Positive Cancer (2017)
  • Author(s): Ito K, Mitsunaga M, Nishimura T, Saruta M, Iwamoto T, Kobayashi H, Tajiri H
  • Journal Title: Bioconjugate Chemistry Volume: 印刷中 Issue: 5 Pages: 1458-1469
  • DOI: 10.1021/acs.bioconjchem.7b00144
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular targeted photoimmunotherapy for HER2-positive human gastric cancer in combination with chemotherapy results in improved treatment outcomes through different cytotoxic mechanisms. (2016)
  • Author(s): Ito K, Mitsunaga M, Arihiro S, Saruta M, Matsuoka M, Kobayashi H, Tajiri H.
  • Journal Title: BMC Cancer Volume: 16 Issue: 1 Pages: 37-37
  • DOI: 10.1186/s12885-016-2072-0
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Combination photoimmunotherapy with monoclonal antibodies recognizing different epitopes of human epidermal growth factor receptor 2: an assessment of phototherapeutic effect based on fluorescence molecular imaging. (2016)
  • Author(s): Ito K, Mitsunaga M, Nishimura T, Kobayashi H, Tajiri H.
  • Journal Title: Oncotarget Volume: 7 Issue: 12 Pages: 14143-52
  • DOI: 10.18632/oncotarget.7490
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Near-infrared molecular imaging guided photochemoimmunotherapy by bifunctional antibody-drug conjugates targeting HER2-positive cancer cells (2017)
  • Author(s): Makoto Mitsunaga, Kimihiro Ito, Takashi Nishimura
  • Organizer: World Molecular Imaging Congress 2017
  • Int'l Joint Research / Invited
• [Presentation] 多機能抗体薬物複合体を用いたHER2特異的近赤外光線療法 (2017)
  • Author(s): 伊藤公博、光永眞人
  • Organizer: 日本癌学会総会
  • Invited
• [Presentation] Strategies to enhance a treatment effect of HER2-targeted theranostic photoimmunotherapy in experimental human gastric cancer (2016)
  • Author(s): Mitsunaga M, Ito K, Nishimura T, Tajiri H
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: アメリカ、サンディエゴ
  • Year and Date: 2016-05-21
  • Int'l Joint Research / Invited
• [Presentation] HER2-targeted near-infrared photoimmunotherapy based on fluorescence molecular imaging in experimental animal model (2016)
  • Author(s): Mitsunaga M
  • Organizer: 日本癌学会総会
  • Place of Presentation: 横浜
  • Int'l Joint Research / Invited
• [Presentation] 蛍光法によるセンチネルリンパ節検出からセンチネルリンパ節微小転移検出を目指して (2015)
  • Author(s): 光永眞人、小林久隆
  • Organizer: 第17回SNNS研究会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2015-11-13
• [Presentation] Molecular targeted theranostic photoimmunotherapy combining two types of monoclonal antibodies targeting different epitopes of HER2: enhanced phototherapeutic effect based on fluorescence molecular imaging (2015)
  • Author(s): Kimihiro Ito, Makoto Mitsunaga, Seiji Arihiro, Masayuki Saruta, Mika Matsuoka, Hisao Tajiri
  • Organizer: World Molecular Imaging Congress 2015
  • Place of Presentation: アメリカ、ホノルル
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] 蛍光プローブを用いた内視鏡分子イメージングの現状と今後の可能性 (2015)
  • Author(s): 光永眞人、炭山和毅、小林雅邦、伊藤公博、西村尚、岩崎哲良ほか
  • Organizer: 第100回日本消化器内視鏡学会関東地方会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-14
• [Presentation] 蛍光分子イメージングをガイドとした光線治療法の開発 (2015)
  • Author(s): 光永眞人、伊藤公博、西村尚、田尻久雄
  • Organizer: 第100回日本消化器内視鏡学会関東地方会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-13
• [Presentation] Molecular Targeted Theranostic Photoimmunochemotherapy for HER2- Positive Human Gastric Cancer in Mice (2015)
  • Author(s): Kimihiro Ito, Makoto Mitsunaga, Seiji Arihiro, Masayuki Saruta, Mika Matsuoka, Hisao Tajiri
  • Organizer: Digestive Disease Week 2015
  • Place of Presentation: アメリカ、ワシントン
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] 血管を標的とする抗体と光増感剤とのコンジュゲート (2018)
  • Inventor(s): 光永眞人
  • Industrial Property Rights Holder: 東京慈恵会医科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-042803
  • Filing Date: 2018