A novel chimpanzee serotype-based adenoviral vector as delivery tool for cancer vaccines.
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.
Peruzzi
Daniela
D
Oncology/Functional Department, IRBM-Merck Research Labs-via Pontina Km30.6, 00040 Pomezia, Rome, Italy.
Dharmapuri
Sridhar
S
Cirillo
Agostino
A
Bruni
Bruno Ercole
BE
Nicosia
Alfredo
A
Cortese
Riccardo
R
Colloca
Stefano
S
Ciliberto
Gennaro
G
La Monica
Nicola
N
Aurisicchio
Luigi
L
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*
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen