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Development of gene therapy vectors for combination radiotherapy of cancer

Scott, Simon D., Marples, B., Bourne, S., Walker, A., Joiner, M.C. (2001) Development of gene therapy vectors for combination radiotherapy of cancer. In: Cancer Gene Therapy. 8 (11). Springer-Nature (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)

Abstract

The combination of gene therapy with radiotherapy offers exciting prospects for the future treatment of cancer. We have been developing radiation - responsive vectors suitable for use with clinical radiation doses. The vectors contain radiation - responsive CArG elements from the human Egr1 gene regulating expression of heterologous genes. The radio -induction of these novel synthetic promoters was assayed using the green fluorescent protein (GFP) reporter gene. Clinically relevant doses of ionising radiation ( 1 – 3 Gy ) were able to induce GFP production 2 – 3 - fold. These promoters were then used to drive the herpes simplex thymidine kinase/ ganciclovir (HSVtk/ GCV) suicide gene system in tumour cell killing assays (Marples et al., 2000; Gene Therapy 7:511 – 517 ). In order to improve efficacy, we have recently examined the effects of CArG number, sequence and spatial arrangement. This data has enabled us to define some important criteria for CArG induction response at these low doses. To provide long -term, constitutive gene expression and to markedly enhance the level of tumour cell killing a novel ‘‘molecular switch’’ scheme based on Cre/ Lox recombination was adopted. This resulted in a substantial enhancement of GFP production and tumour cell killing ( Scott et al., 2000; Gene Therapy 7:1121 – 1125 ). To further improve the overall efficiency of the switch scheme, the original dual - plasmid system has now been replaced with a single vector bearing all the active components. This vector is currently being tested in a U87 glioblastoma xenograft model.

Item Type: Conference or workshop item (Poster)
Subjects: R Medicine
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Simon Scott
Date Deposited: 03 Dec 2017 15:21 UTC
Last Modified: 29 May 2019 13:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45889 (The current URI for this page, for reference purposes)
Scott, Simon D.: https://orcid.org/0000-0002-8290-0461
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