Trastuzumab-based photoimmunotherapy integrated with viral HER2 transduction inhibits peritoneally disseminated HER2-negative cancer

Michihiro Ishida, Shunsuke Kagawa, Kyoko Shimoyama, Kiyoto Takehara, Kazuhiro Noma, Shunsuke Tanabe, Yasuhiro Shirakawa, Hiroshi Tazawa, Hisataka Kobayashi, Toshiyoshi Fujiwara

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Abstract

Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of treatments for peritoneal dissemination of gastric cancer.Wehypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumabbased photoimmunotherapy (PIT) might provide excellent and selective antitumor effects for peritoneal dissemination of gastric cancer. In vitro, adenovirus/HER2-ECD (Ad/HER2-ECD) efficiently transduced HER2-ECD into HER2-negative gastric cancer cells. Trastuzumab-IR700 (Tra-IR700)-mediated PIT induced selective cell death of HER2-ECD-transduced tumor cells. Ad/HER2-ECD also induced homogenous expression of HER2 in heterogeneous gastric cancer cells, resulting in uniform sensitivity of the cells to Tra-IR700-mediated PIT. 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 bearing MKN45. Furthermore, minimal side effects allowed the integrated therapy to be used repeatedly, providing better control of peritoneal dissemination. In conclusion, the novel therapy of molecular-targeted PIT integrated with gene transfer technology is a promising approach for the treatment of peritoneal dissemination in gastric cancer.

Original languageEnglish
Pages (from-to)402-411
Number of pages10
JournalMolecular Cancer Therapeutics
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

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Stomach Neoplasms
Neoplasms
Adenoviridae
Molecular Targeted Therapy
Neoplasm Metastasis
Genes
Technology Transfer
Trastuzumab
Cell Death
Therapeutics
Antigens

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "Trastuzumab-based photoimmunotherapy integrated with viral HER2 transduction inhibits peritoneally disseminated HER2-negative cancer",
abstract = "Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of treatments for peritoneal dissemination of gastric cancer.Wehypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumabbased photoimmunotherapy (PIT) might provide excellent and selective antitumor effects for peritoneal dissemination of gastric cancer. In vitro, adenovirus/HER2-ECD (Ad/HER2-ECD) efficiently transduced HER2-ECD into HER2-negative gastric cancer cells. Trastuzumab-IR700 (Tra-IR700)-mediated PIT induced selective cell death of HER2-ECD-transduced tumor cells. Ad/HER2-ECD also induced homogenous expression of HER2 in heterogeneous gastric cancer cells, resulting in uniform sensitivity of the cells to Tra-IR700-mediated PIT. 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 bearing MKN45. Furthermore, minimal side effects allowed the integrated therapy to be used repeatedly, providing better control of peritoneal dissemination. In conclusion, the novel therapy of molecular-targeted PIT integrated with gene transfer technology is a promising approach for the treatment of peritoneal dissemination in gastric cancer.",
author = "Michihiro Ishida and Shunsuke Kagawa and Kyoko Shimoyama and Kiyoto Takehara and Kazuhiro Noma and Shunsuke Tanabe and Yasuhiro Shirakawa and Hiroshi Tazawa and Hisataka Kobayashi and Toshiyoshi Fujiwara",
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AU - Ishida, Michihiro

AU - Kagawa, Shunsuke

AU - Shimoyama, Kyoko

AU - Takehara, Kiyoto

AU - Noma, Kazuhiro

AU - Tanabe, Shunsuke

AU - Shirakawa, Yasuhiro

AU - Tazawa, Hiroshi

AU - Kobayashi, Hisataka

AU - Fujiwara, Toshiyoshi

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