title: Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells.
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.
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimoyama
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kagawa
authors.forename: Michihiro
authors.initials: M
authors.lastname: Ishida
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Noma
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Takehara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanabe
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuoka
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy; D007211:Indoles / Q000008:administration & dosage; D007259:Infrared Rays; D061986:MCF-7 Cells; D017646:Organosilicon Compounds / Q000008:administration & dosage; D017319:Photosensitizing Agents / Q000008:administration & dosage; D010789:Phototherapy; D017434:Protein Structure, Tertiary / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014161:Transduction, Genetic; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000593031:IR700DX-mbc94; C508053:ERBB2 protein, human