title: Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma.
abstract: Fluorescence-guided surgery (FGS) of cancer is an area of intense interest. However, FGS of cancer has not yet been shown to be curative due to residual microscopic disease. Human fibrosarcoma HT1080 expressing red fluorescent protein (RFP) was implanted orthotopically in the quadriceps femoris muscle of nude mice. The tumor-bearing mice were injected with high and low-dose telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401, which labeled the tumor with GFP. Fluorescence-guided surgery (FGS) or bright light surgery (BLS) was then performed. OBP-401 could label soft-tissue sarcoma (STS) with GFP in situ, concordant with RFP. OBP-401-based FGS resulted in superior resection of STS in the orthotopic model of soft-tissue sarcoma, compared to BLS. High-dose administration of OBP-401 enabled FGS without residual sarcoma cells or local or metastatic recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. High-dose OBP-401 based-FGS improved disease free survival (p = 0.00049) as well as preserved muscle function compared with BLS. High-dose OBP-401-based FGS could cure STS, a presently incurable disease. Since the parent virus of OBP-401, OBP-301, has been previously proven safe in a Phase I clinical trial, it is expected the OBP-401-FGS technology described in the present report should be translatable to the clinic in the near future.
authors.affiliation: 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.
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.affiliation: Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.affiliation: Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Toneri
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
authors.forename: Mako
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Oncolys BioPharm Inc., Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Urata
authors.affiliation: Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kagawa
authors.affiliation: Department of Surgery, University of California San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California San Diego, CA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005453:Fluorescence; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D049408:Luminescent Agents; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D012513:Sarcoma, Experimental / Q000235:genetics / Q000601:surgery*; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000601:surgery*; D025321:Surgery, Computer-Assisted; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D049408:Luminescent Agents; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
keywords: OBP-401; adenovirus; fluorescence-guided surgery (FGS); nude mice; soft tissue sarcoma