Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent

强力霉素诱导的黑色素生成痘苗病毒作为治疗诊断抗癌剂

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作者:Lorenz Kirscher, Xosé Luis Deán-Ben, Miriam Scadeng, Angelika Zaremba, Qian Zhang, Christina Kober, Thomas Felix Fehm, Daniel Razansky, Vasilis Ntziachristos, Jochen Stritzker, Aladar A Szalay

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.

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