Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models

Shuya Yano; Kiyoto Takehara; Hiroyuki Kishimoto; Yasuo Urata; Shunsuke Kagawa; Michael Bouvet; Toshiyoshi Fujiwara; Robert M. Hoffman

doi:10.18632/oncotarget.6670

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Research Papers:

Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models

Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara and Robert M. Hoffman _

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Oncotarget. 2016; 7:18558-18572. https://doi.org/10.18632/oncotarget.6670

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Abstract

Shuya Yano1,2,3, Kiyoto Takehara1,2,3, Hiroyuki Kishimoto3, Yasuo Urata4, Shunsuke Kagawa3, Michael Bouvet2, Toshiyoshi Fujiwara3, Robert M. Hoffman1,2

1AntiCancer, Inc., San Diego, CA, USA

2Department of Surgery, University of California San Diego, La Jolla, CA, USA

3Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

4Oncolys BioPharm Inc., Tokyo, Japan

Correspondence to:

Robert M. Hoffman, e-mail: [email protected]

Toshiyoshi Fujiwara, e-mail: [email protected]

Keywords: melanoma, nude mice, fluorescence-guided surgery (FGS), adenovirus, OBP-401

Abbreviations: GFP, green fluorescent protein; RFP, red fluorescent protein; FGS, fluorescence-guided surgery; BLS, bright-light surgery

Received: September 17, 2015 Accepted: November 27, 2015 Published: December 18, 2015

ABSTRACT

Malignant melanoma requires precise resection in order to avoid metastatic recurrence. We report here that the telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401 could label malignant melanoma with GFP in situ in orthotopic mouse models. OBP-401-based fluorescence-guided surgery (FGS) resulted in the complete resection of malignant melanoma in the orthotopic models, where conventional bright-light surgery (BLS) could not. High-dose administration of OBP-401 enabled FGS without residual cancer cells or recurrence, due to its dual effect of cancer-cell labeling with GFP and killing.

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Research Papers:

Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models

Abstract