Drug-Encoded Biomarkers for Monitoring Biological Therapies

PloS One
Desislava TsonevaAladar A Szalay

Abstract

Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. Here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from E. coli (GusA) and Staphylococcus sp. RLH1 (GusPlus), and the luciferase from Gaussia princeps (GLuc). The three genes encoding these proteins were inserted individually into vaccinia virus GLV-1h68 genome under the control of an identical promoter. The three resulting recombinant viruses were used to infect tumor cells in cultures and human tumor xenografts in nude mice. In contrast to the actively secreted GLuc, the cytoplasmic glucuronidases GusA and GusPlus were released into the supernatants only as a result of virus-mediated oncolysis. GusPlus resulted in the most sensitive detection of enzyme activity under controlled assay conditions in samples containing as little as 1 pg/ml of GusPlus, followed by GusA (25 pg/ml) and GLuc (≥375 pg/ml). Unexpectedly, even though GusA had a lower specific activity compared to GusPlus, the substrate conversion in the serum of tumor-bearing mice injected with the GusA-encoding virus strains was ...Continue Reading

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Feb 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jochen StritzkerAladar A Szalay

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Citations

Jul 12, 2019·Nature Reviews. Drug Discovery·Kevin HarringtonJean-Charles Soria

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Datasets Mentioned

BETA
AAG54095.1
AAK29422.1

Methods Mentioned

BETA
Assay
protein assay
ELISA

Software Mentioned

ImageJ
PK
GenScript
Molecular Imaging
Excel
Excel®
GusPlus

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