Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells

Kyoko Shimoyama, Shunsuke Kagawa, Michihiro Ishida, Shinichiro Watanabe, Kazuhiro Noma, Kiyoto Takehara, Hiroshi Tazawa, Yuuri Hashimoto, Shunsuke Tanabe, Junji Matsuoka, Hisataka Kobayashi, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The prognosis of HER2-positive breast cancer has been improved by trastuzumab therapy, which features high specificity and limited side effects. However, trastuzumab-based therapy has shortcomings. Firstly, HER2-targeted therapy is only applicable to HER2-expressing tumors, which comprise only 20–25 % of primary breast cancers. Secondly, many patients who initially respond to trastuzumab ultimately develop disease progression. To overcome these problems, we employed virus-mediated HER2 transduction and photoimmunotherapy (PIT) which involves trastuzumab conjugated with a photosensitizer, trastuzumab-IR700, and irradiation of near-infrared light. We hypothesized that the gene transduction technique together with PIT would expand the range of tumor entities suitable for trastuzumab-based therapy and improve its antitumor activity. The HER2-extracellular domain (ECD) was transduced by the adenoviral vector, Ad-HER2-ECD, and PIT with trastuzumab-IR700 was applied in the HER2-negative cancer cells. Ad-HER2-ECD can efficiently transduce HER2-ECD into HER2-negative human cancer cells. PIT with trastuzumab-IR700 induced direct cell membrane destruction of Ad-HER2-ECD-transduced HER2-negative cancer cells. Novel combination of viral transduction of a target antigen and an antibody-based PIT would expand and potentiate molecular-targeted therapy even for target-negative or attenuated cancer cells.

Original languageEnglish
Pages (from-to)597-605
Number of pages9
JournalBreast Cancer Research and Treatment
Volume149
Issue number3
DOIs
Publication statusPublished - 2015

Fingerprint

Breast Neoplasms
Neoplasms
Molecular Targeted Therapy
Photosensitizing Agents
Trastuzumab
Therapeutics
Disease Progression
Cell Membrane
Viruses
Light
Antigens
Antibodies
Genes

Keywords

  • Adenovirus
  • Breast cancer
  • HER2
  • Photoimmunotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells. / Shimoyama, Kyoko; Kagawa, Shunsuke; Ishida, Michihiro; Watanabe, Shinichiro; Noma, Kazuhiro; Takehara, Kiyoto; Tazawa, Hiroshi; Hashimoto, Yuuri; Tanabe, Shunsuke; Matsuoka, Junji; Kobayashi, Hisataka; Fujiwara, Toshiyoshi.

In: Breast Cancer Research and Treatment, Vol. 149, No. 3, 2015, p. 597-605.

Research output: Contribution to journalArticle

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