Comparative evaluation of preclinical in vivo models for the assessment of replicating retroviral vectors for the treatment of glioblastoma.

Journal of Neuro-oncology
J HlavatýMatthias Renner

Abstract

Despite impressive improvements in neurosurgical techniques, radiation and chemotherapy during the past few years, little progress has been made in the treatment of malignant gliomas. Recently, the efficacy of suicide gene therapy based on replication-competent retroviral (RCR) vectors as delivery vehicles for the therapeutic gene has been described in the treatment of experimental cancer, including gliomas. In this study, we have thus critically evaluated a panel of human and rodent glioma/glioblastoma cell lines (U-87MG, U-118MG, LN-18, LN-229, 8-MG-BA, 42-MG-BA, A-172, T-98G, UVW, C6, 9L, G-26, GL-261, Tu-2449, Tu-9648) with respect to RCR virus vector spread, sensitivity towards the cytosine deaminase (CD)/5-flurocytosine (5-FC)/5-flurouracil (5-FU) suicide system, and orthotopic growth characteristics in mice to identify suitable preclinical animal models for the development of a glioblastoma gene therapy. Rapid virus spread was observed in eight out of nine human cell lines tested in vitro. As expected, only CD-expressing cells became sensitive to 5-FC, due to their ability to convert the prodrug in its toxic form, 5-FU. All LD(50) values were within the range of concentrations obtained in human body fluids after conventi...Continue Reading

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Citations

Jun 10, 2020·Biomedicines·Verena J HerbenerHannah Strobel
May 23, 2015·Human Vaccines & Immunotherapeutics·Pascal R A BuijsBernadette G van den Hoogen
Nov 30, 2019·Neurosurgical Review·Ryota TamuraMasahiro Toda
Feb 21, 2013·Journal of Neuro-oncology·Jessica S HaberJohn A Boockvar
Mar 15, 2013·Neuro-oncology·Maike PriesterJakob Weissenberger
Mar 17, 2021·Expert Opinion on Biological Therapy·Sara A CollinsDouglas J Jolly
Apr 4, 2021·Cells·William H HicksKalil G Abdullah
Jan 6, 2012·Journal of Translational Medicine·Sandeep S PatilAladar A Szalay

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