title: A polyepitope DNA vaccine targeted to Her-2/ErbB-2 elicits a broad range of human and murine CTL effectors to protect against tumor challenge.
abstract: A cDNA vaccine (pVax1/pet-neu) was designed to encode 12 different Her-2/ErbB-2-derived, HLA-A*0201-restricted dominant and high-affinity heteroclitic cryptic epitopes. Vaccination with pVax1/pet-neu triggered multiple and ErbB-2-specific CTL responses in HLA-A*0201 transgenic HHD mice and in HLA-A*0201 healthy donors in vitro. Human and murine CTL specific for each one of the 12 ErbB-2 peptides recognized in vitro both human and murine tumor cells overexpressing endogenous ErbB-2. Furthermore, vaccination of HHD mice with pVax1/pet-neu significantly delayed the in vivo growth of challenged ErbB-2-expressing tumor (EL4/HHD/neu murine thymoma) more actively when compared with vaccination with the empty vector (pVax1) or vehicle alone. These data indicate that the pVax1/pet-neu cDNA vaccine coding for a poly-ErbB-2 epitope is able to generate simultaneous ErbB-2-specific antitumor responses against dominant and cryptic multiple epitopes.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U753, Institut Gustave Roussy, Villejuif, France. antoscardo@yahoo.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Scardino
authors.forename: Maurizio
authors.initials: M
authors.lastname: Alimandi
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Correale
authors.forename: Steven G
authors.initials: SG
authors.lastname: Smith
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Firat
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cusi
authors.forename: Olivier
authors.initials: O
authors.lastname: Faure
authors.forename: Stephanie
authors.initials: S
authors.lastname: Graf-Dubois
authors.forename: Giulia
authors.initials: G
authors.lastname: Cencioni
authors.forename: Jordan
authors.initials: J
authors.lastname: Marrocco
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Andrew Michael
authors.initials: AM
authors.lastname: Jackson
authors.forename: Kostas
authors.initials: K
authors.lastname: Kosmatopoulos
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000737:chemistry*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D013945:Thymoma / Q000378:metabolism; D019444:Vaccines, DNA / Q000737:chemistry*
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA