title: Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent.
abstract: We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.
authors.affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Kirscher
authors.affiliation: 4. Helmholtz Institute, IBMI, Ingolstädter Landstraße 1, 85764 Oberschleißheim, Germany.
authors.forename: Xosé Luis
authors.initials: XL
authors.lastname: Deán-Ben
authors.affiliation: 3. University of San Diego, Center of Functional MRI, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Scadeng
authors.affiliation: 4. Helmholtz Institute, IBMI, Ingolstädter Landstraße 1, 85764 Oberschleißheim, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Zaremba
authors.affiliation: 2. Genelux Cooperation, San Diego Science Center, 3030 Bunker Hill St, San Diego, CA 92109, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kober
authors.affiliation: 4. Helmholtz Institute, IBMI, Ingolstädter Landstraße 1, 85764 Oberschleißheim, Germany.
authors.forename: Thomas Felix
authors.initials: TF
authors.lastname: Fehm
authors.affiliation: 4. Helmholtz Institute, IBMI, Ingolstädter Landstraße 1, 85764 Oberschleißheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Razansky
authors.affiliation: 4. Helmholtz Institute, IBMI, Ingolstädter Landstraße 1, 85764 Oberschleißheim, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany ; 2. Genelux Cooperation, San Diego Science Center, 3030 Bunker Hill St, San Diego, CA 92109, USA.
authors.forename: Jochen
authors.initials: J
authors.lastname: Stritzker
authors.affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany ; 2. Genelux Cooperation, San Diego Science Center, 3030 Bunker Hill St, San Diego, CA 92109, USA ; 5. Department of Radiation Oncology, Moores Cancer Center, University of California, La Jolla, CA 92093, USA.
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004318:Doxycycline / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000295:instrumentation / Q000379:methods*; D011859:Radiography; D000068936:Theranostic Nanomedicine / Q000295:instrumentation / Q000379:methods*; D047368:Tumor Burden; D014616:Vaccinia virus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
chemical_list: D008543:Melanins; D014442:Monophenol Monooxygenase; D004318:Doxycycline
keywords: Molecular Imaging; Oncolysis; Reporter gene; virotherapy