title: An Ad5[E1-, E2b-]-HER2/neu vector induces immune responses and inhibits HER2/neu expressing tumor progression in Ad5 immune mice.
abstract: Immunotherapy is a promising approach for the treatment of cancers. Modified adenovirus 5 (Ad5) vectors have been used as a platform to deliver genes encoding tumor associated antigens (TAA). A major obstacle to Ad5 vector immunotherapy has been the induction of vector immunity following administration or the presence of pre-existing Ad5 immunity, which results in vector mitigation. It has been reported by us that the Ad5[E1-, E2b-] platform with unique deletions in the E1, E2b and E3 regions can induce potent cell mediated immunity (CMI) against delivered transgene products in the presence of pre-existing Ad5 immunity. Here we report the use of an Ad5[E1-, E2b-] vector platform expressing the TAA HER2/neu as a breast cancer immunotherapeutic agent. Ad5[E1-, E2b-]-HER2/neu induced potent CMI against HER2/neu in Ad5 naïve and Ad5 immune mice. Humoral responses were also induced and antibodies could lyse HER2/neu expressing tumor cells in the presence of complement in vitro. Ad5[E1-, E2b-]-HER2/neu prevented establishment of HER2/neu-expressing tumors and significantly inhibited progression of established tumors in Ad5 naïve and Ad5 immune murine models. These data demonstrate that in vivo delivery of Ad5[E1-, E2b-]-HER2/neu can induce anti-TAA immunity and inhibit progression of HER2/neu expressing cancers.
authors.affiliation: Etubics Corporation, Seattle, WA 98119, USA. beth@etubics.com
authors.forename: E S
authors.initials: ES
authors.lastname: Gabitzsch
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Balcaitis
authors.forename: J P
authors.initials: JP
authors.lastname: Balint
authors.forename: F R
authors.initials: FR
authors.lastname: Jones
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D019076:Transgenes / Q000235:genetics
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse