Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent

Theranostics. 2015 Jun 15;5(10):1045-57. doi: 10.7150/thno.12533. eCollection 2015.

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: Molecular Imaging; Oncolysis; Reporter gene; virotherapy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Doxycycline / pharmacology
  • Gene Expression Regulation, Viral / drug effects
  • Genetic Vectors / genetics*
  • Genetic Vectors / metabolism
  • Genetic Vectors / pharmacology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Melanins / biosynthesis*
  • Mice
  • Mice, Nude
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Neoplasms / diagnosis
  • Neoplasms / diagnostic imaging
  • Neoplasms / therapy*
  • Neoplasms / virology
  • Oncolytic Virotherapy / instrumentation
  • Oncolytic Virotherapy / methods*
  • Radiography
  • Theranostic Nanomedicine / instrumentation
  • Theranostic Nanomedicine / methods*
  • Tumor Burden
  • Vaccinia virus / drug effects
  • Vaccinia virus / enzymology
  • Vaccinia virus / genetics*
  • Vaccinia virus / metabolism

Substances

  • Melanins
  • Monophenol Monooxygenase
  • Doxycycline