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.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kottke
authors.forename: Fiona
authors.initials: F
authors.lastname: Errington
authors.forename: Jose
authors.initials: J
authors.lastname: Pulido
authors.forename: Feorillo
authors.initials: F
authors.lastname: Galivo
authors.forename: Jill
authors.initials: J
authors.lastname: Thompson
authors.forename: Phonphimon
authors.initials: P
authors.lastname: Wongthida
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Diaz
authors.forename: Heung
authors.initials: H
authors.lastname: Chong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ilett
authors.forename: John
authors.initials: J
authors.lastname: Chester
authors.forename: Hardev
authors.initials: H
authors.lastname: Pandha
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.forename: Peter
authors.initials: P
authors.lastname: Selby
authors.forename: Alan
authors.initials: A
authors.lastname: Melcher
authors.forename: Richard
authors.initials: R
authors.lastname: Vile
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D005822:Genetic Vectors / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000628:therapy; D018116:Vesiculovirus / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018076:DNA, Complementary