title: A novel chimpanzee serotype-based adenoviral vector as delivery tool for cancer vaccines.
abstract: The use of adenovirus (Ad) as vaccine vectors is hindered by pre-existing immunity to human Ads in most of the human population. In order to overcome this limitation, uncommon alternative Ad serotypes need to be utilized. In this study, an E1-E3 deleted recombinant Ad based on the chimpanzee serotype 3 (ChAd3) was engineered to express human carcinoembryonic antigen (CEA) protein or rat neu extracellular/transmembrane domains (ECD.TM). ChAd3 vectors were tested in CEA transgenic (CEA.Tg) and BALB/NeuT mice, which show immunologic tolerance to these antigens. ChAd3 is capable of inducing an immune response comparable to that of hAd5 serotype-based vectors, thus breaking tolerance to tumor associated antigens (TAAs) and achieving anti-tumor effects. Of importance is that ChAd3 can overcome hAd5 pre-existing immunity and work in conjunction with DNA electroporation (DNA-EP) and other Ad vaccines based on common human serotypes.
authors.affiliation: Oncology/Functional Department, IRBM-Merck Research Labs-via Pontina Km30.6, 00040 Pomezia, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Peruzzi
authors.forename: Sridhar
authors.initials: S
authors.lastname: Dharmapuri
authors.forename: Agostino
authors.initials: A
authors.lastname: Cirillo
authors.forename: Bruno Ercole
authors.initials: BE
authors.lastname: Bruni
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D007109:Immunity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D002679:Pan troglodytes / Q000235:genetics / Q000276:immunology*; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen