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

Kottke, Timothy, Errington, Fiona, Pulido, Jose, Galivo, Feorillo, Thompson, Jill, Wongthida, P., Diaz, Rosa Maria, Chong, Heung, llett, Elizabeth, Chester, John D., Pandha, Hardev, Harrington, Kevin, Selby, Peter, Melcher, Alan and Vile, Richard 2011. Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. Nature Medicine 17 (7) , pp. 854-859. 10.1038/nm.2390.

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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
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: Nature Publishing Group
ISSN: 1078-8956
Funders: The Richard M. Schulze Family Foundation, The Mayo Foundation, Cancer Research UK, US National Institutes of Health grants R01 CA107082, R01 CA130878 and R01 CA132734, Terry and Judith Paul.
Last Modified: 04 Jun 2017 05:37
URI: http://orca-mwe.cf.ac.uk/id/eprint/52501

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