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Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors.

Kottke, T, Errington, F, Pulido, J, Galivo, F, Thompson, J, Wongthida, P, Diaz, RM, Chong, H, Ilett, E, Chester, J , Pandha, H, Harrington, K, Selby, P, Melcher, A and Vile, R (2011) Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. Nat Med, 17 (7). pp. 854-859.

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Abstract

Effective cancer immunotherapy requires the release of a broad spectrum of tumor antigens in the context of potent immune activation. We show here that a cDNA library of normal tissue, expressed from a highly immunogenic viral platform, cures established tumors of the same histological type from which the cDNA library was derived. Immune escape occurred with suboptimal vaccination, but tumor cells that escaped the immune pressure were readily treated by second-line virus-based immunotherapy. This approach has several major advantages. Use of the cDNA library leads to presentation of a broad repertoire of (undefined) tumor-associated antigens, which reduces emergence of treatment-resistant variants and also permits rational, combined-modality approaches in the clinic. Finally, the viral vectors can be delivered systemically, without the need for tumor targeting, and are amenable to clinical-grade production. Therefore, virus-expressed cDNA libraries represent a novel paradigm for cancer treatment addressing many of the key issues that have undermined the efficacy of immuno- and virotherapy to date.

Item Type: Article
Authors :
NameEmailORCID
Kottke, TUNSPECIFIEDUNSPECIFIED
Errington, FUNSPECIFIEDUNSPECIFIED
Pulido, JUNSPECIFIEDUNSPECIFIED
Galivo, FUNSPECIFIEDUNSPECIFIED
Thompson, JUNSPECIFIEDUNSPECIFIED
Wongthida, PUNSPECIFIEDUNSPECIFIED
Diaz, RMUNSPECIFIEDUNSPECIFIED
Chong, HUNSPECIFIEDUNSPECIFIED
Ilett, EUNSPECIFIEDUNSPECIFIED
Chester, JUNSPECIFIEDUNSPECIFIED
Pandha, Hh.pandha@surrey.ac.ukUNSPECIFIED
Harrington, KUNSPECIFIEDUNSPECIFIED
Selby, PUNSPECIFIEDUNSPECIFIED
Melcher, AUNSPECIFIEDUNSPECIFIED
Vile, RUNSPECIFIEDUNSPECIFIED
Date : July 2011
Identification Number : 10.1038/nm.2390
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:32
Last Modified : 17 May 2017 14:43
URI: http://epubs.surrey.ac.uk/id/eprint/824133

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