TY - JOUR
T1 - Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells
AU - Shimoyama, Kyoko
AU - Kagawa, Shunsuke
AU - Ishida, Michihiro
AU - Watanabe, Shinichiro
AU - Noma, Kazuhiro
AU - Takehara, Kiyoto
AU - Tazawa, Hiroshi
AU - Hashimoto, Yuuri
AU - Tanabe, Shunsuke
AU - Matsuoka, Junji
AU - Kobayashi, Hisataka
AU - Fujiwara, Toshiyoshi
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/2
Y1 - 2015/2
N2 - 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.
AB - 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.
KW - Adenovirus
KW - Breast cancer
KW - HER2
KW - Photoimmunotherapy
UR - http://www.scopus.com/inward/record.url?scp=84925497608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925497608&partnerID=8YFLogxK
U2 - 10.1007/s10549-015-3265-y
DO - 10.1007/s10549-015-3265-y
M3 - Article
C2 - 25616354
AN - SCOPUS:84925497608
SN - 0167-6806
VL - 149
SP - 597
EP - 605
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -