Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence.
We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model.
AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.|Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shuya
S
Yano
AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.|Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kiyoto
K
Takehara
AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
Shinji
S
Miwa
Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hiroyuki
H
Kishimoto
Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
Hiroshi
H
Tazawa
Oncolys BioPharm Inc., Tokyo, Japan.
Yasuo
Y
Urata
Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shunsuke
S
Kagawa
Department of Surgery, University of California San Diego, CA, USA.
Michael
M
Bouvet
Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Toshiyoshi
T
Fujiwara
AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
Robert M
RM
Hoffman
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D061848:Optical Imaging / Q000379:methods; D012008:Recurrence; D025321:Surgery, Computer-Assisted / Q000379:methods; D014161:Transduction, Genetic; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery*; D023041:Xenograft Model Antitumor Assays
D049452:Green Fluorescent Proteins
GFP/RFP; adenovirus; fluorescence-guided surgery (FGS); survival; telomerase dependent
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