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

Timothy Kottke, Fiona Errington, Jose S Pulido, Feorillo Galivo, Jill Thompson, Phonphimon Wongthida, Rosa Maria Diaz, Heung Chong, Elizabeth Ilett, John Chester, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Geoffrey Vile

Research output: Contribution to journalArticle

64 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)854-859
Number of pages6
JournalNature Medicine
Volume17
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Gene Library
Viruses
Tumors
Vaccination
Neoplasm Antigens
Neoplasms
Immunotherapy
Oncology
Chemical activation
Cells
Tissue
Antigens
Pressure
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. / Kottke, Timothy; Errington, Fiona; Pulido, Jose S; Galivo, Feorillo; Thompson, Jill; Wongthida, Phonphimon; Diaz, Rosa Maria; Chong, Heung; Ilett, Elizabeth; Chester, John; Pandha, Hardev; Harrington, Kevin; Selby, Peter; Melcher, Alan; Vile, Richard Geoffrey.

In: Nature Medicine, Vol. 17, No. 7, 07.2011, p. 854-859.

Research output: Contribution to journalArticle

Kottke, T, Errington, F, Pulido, JS, Galivo, F, Thompson, J, Wongthida, P, Diaz, RM, Chong, H, Ilett, E, Chester, J, Pandha, H, Harrington, K, Selby, P, Melcher, A & Vile, RG 2011, 'Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors', Nature Medicine, vol. 17, no. 7, pp. 854-859. https://doi.org/10.1038/nm.2390
Kottke, Timothy ; Errington, Fiona ; Pulido, Jose S ; Galivo, Feorillo ; Thompson, Jill ; Wongthida, Phonphimon ; Diaz, Rosa Maria ; Chong, Heung ; Ilett, Elizabeth ; Chester, John ; Pandha, Hardev ; Harrington, Kevin ; Selby, Peter ; Melcher, Alan ; Vile, Richard Geoffrey. / Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. In: Nature Medicine. 2011 ; Vol. 17, No. 7. pp. 854-859.
@article{87e9ac98908846eabcaa7969a94810d4,
title = "Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors",
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.",
author = "Timothy Kottke and Fiona Errington and Pulido, {Jose S} and Feorillo Galivo and Jill Thompson and Phonphimon Wongthida and Diaz, {Rosa Maria} and Heung Chong and Elizabeth Ilett and John Chester and Hardev Pandha and Kevin Harrington and Peter Selby and Alan Melcher and Vile, {Richard Geoffrey}",
year = "2011",
month = "7",
doi = "10.1038/nm.2390",
language = "English (US)",
volume = "17",
pages = "854--859",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors

AU - Kottke, Timothy

AU - Errington, Fiona

AU - Pulido, Jose S

AU - Galivo, Feorillo

AU - Thompson, Jill

AU - Wongthida, Phonphimon

AU - Diaz, Rosa Maria

AU - Chong, Heung

AU - Ilett, Elizabeth

AU - Chester, John

AU - Pandha, Hardev

AU - Harrington, Kevin

AU - Selby, Peter

AU - Melcher, Alan

AU - Vile, Richard Geoffrey

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79960125220&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960125220&partnerID=8YFLogxK

U2 - 10.1038/nm.2390

DO - 10.1038/nm.2390

M3 - Article

C2 - 21685898

AN - SCOPUS:79960125220

VL - 17

SP - 854

EP - 859

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 7

ER -