University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Synergistic cytotoxicity of oncolytic reovirus in combination with cisplatin-paclitaxel doublet chemotherapy.

Roulstone, V, Twigger, K, Zaidi, S, Pencavel, T, Kyula, JN, White, C, McLaughlin, M, Seth, R, Karapanagiotou, EM, Mansfield, D , Coffey, M, Nuovo, G, Vile, RG, Pandha, HS, Melcher, AA and Harrington, KJ (2012) Synergistic cytotoxicity of oncolytic reovirus in combination with cisplatin-paclitaxel doublet chemotherapy. Gene Ther.

Full text not available from this repository.

Abstract

Oncolytic reovirus is currently under active investigation in a range of tumour types. Early phase studies have shown that this agent has modest monotherapy efficacy and its future development is likely to focus on combination regimens with cytotoxic chemotherapy. Indeed, phase I/II clinical trials have confirmed that reovirus can be safely combined with cytotoxic drugs, including a platin-taxane doublet regimen, which is currently being tested in a phase III clinical trial in patients with relapsed/metastatic head and neck cancer. Therefore, we have tested this triple (reovirus, cisplatin, paclitaxel) combination therapy in a panel of four head and neck cancer cell lines. Using the combination index (CI) method, the triple therapy demonstrated synergistic cytotoxicity in vitro in both malignant and non-malignant cell lines. In head and neck cancer cell lines, this was associated with enhanced caspase 3 and 7 cleavage, but no increase in viral replication. In vitro analyses confirmed colocalisation of markers of reovirus infection and caspase 3. Triple therapy was significantly more effective than reovirus or cisplatin-paclitaxel in athymic nude mice. These data suggest that the combination of reovirus plus platin-taxane doublet chemotherapy has significant activity in head and neck cancer and underpin the current phase III study in this indication.Gene Therapy advance online publication, 16 August 2012; doi:10.1038/gt.2012.68.

Item Type: Article
Authors :
NameEmailORCID
Roulstone, VUNSPECIFIEDUNSPECIFIED
Twigger, KUNSPECIFIEDUNSPECIFIED
Zaidi, SUNSPECIFIEDUNSPECIFIED
Pencavel, TUNSPECIFIEDUNSPECIFIED
Kyula, JNUNSPECIFIEDUNSPECIFIED
White, CUNSPECIFIEDUNSPECIFIED
McLaughlin, MUNSPECIFIEDUNSPECIFIED
Seth, RUNSPECIFIEDUNSPECIFIED
Karapanagiotou, EMUNSPECIFIEDUNSPECIFIED
Mansfield, DUNSPECIFIEDUNSPECIFIED
Coffey, MUNSPECIFIEDUNSPECIFIED
Nuovo, GUNSPECIFIEDUNSPECIFIED
Vile, RGUNSPECIFIEDUNSPECIFIED
Pandha, HSh.pandha@surrey.ac.ukUNSPECIFIED
Melcher, AAUNSPECIFIEDUNSPECIFIED
Harrington, KJUNSPECIFIEDUNSPECIFIED
Date : 16 August 2012
Identification Number : 10.1038/gt.2012.68
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:45
Last Modified : 17 May 2017 14:44
URI: http://epubs.surrey.ac.uk/id/eprint/824977

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800