Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence
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Shuya Yano1,2,3, Kiyoto Takehara1,2,3, Shinji Miwa1,2, Hiroyuki Kishimoto3, Hiroshi Tazawa4, Yasuo Urata5, Shunsuke Kagawa3, Michael Bouvet2, Toshiyoshi Fujiwara3, Robert M. Hoffman1,2
1AntiCancer, Inc., San Diego, CA, USA
2Department of Surgery, University of California San Diego, CA, USA
3Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
4Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
5Oncolys BioPharm Inc., Tokyo, Japan
Robert M. Hoffman, email: [email protected]
Toshiyoshi Fujiwara, email: toshi_ [email protected]
Keywords: fluorescence-guided surgery (FGS), telomerase dependent, adenovirus, GFP/RFP, survival
Received: July 07, 2016 Accepted: September 06, 2016 Published: September 28, 2016
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.
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