Theranostics 2015; 5(10):1045-1057. doi:10.7150/thno.12533

Research Paper

Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent

Lorenz Kirscher1, Xosé Luis Deán-Ben4, Miriam Scadeng3, Angelika Zaremba4, Qian Zhang2, Christina Kober1, Thomas Felix Fehm4, Daniel Razansky4, Vasilis Ntziachristos4, Jochen Stritzker1,2,✉, Aladar A. Szalay1,2,5,✉

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
3. University of San Diego, Center of Functional MRI, 9500 Gilman Drive, La Jolla, CA 92093, USA
4. Helmholtz Institute, IBMI, Ingolstädter Landstraße 1, 85764 Oberschleißheim, Germany
5. Department of Radiation Oncology, Moores Cancer Center, University of California, La Jolla, CA 92093, USA

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Citation:
Kirscher L, Deán-Ben XL, Scadeng M, Zaremba A, Zhang Q, Kober C, Fehm TF, Razansky D, Ntziachristos V, Stritzker J, Szalay AA. Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent. Theranostics 2015; 5(10):1045-1057. doi:10.7150/thno.12533. Available from http://www.thno.org/v05p1045.htm

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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.

Keywords: Oncolysis, Molecular Imaging, Reporter gene, virotherapy