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.
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.
Scardino
Antonio
A
Institut National de la Santé et de la Recherche Médicale U753, Institut Gustave Roussy, Villejuif, France. antoscardo@yahoo.it
Alimandi
Maurizio
M
Correale
Pierpaolo
P
Smith
Steven G
SG
Bei
Roberto
R
Firat
Hüseyin
H
Cusi
Maria Grazia
MG
Faure
Olivier
O
Graf-Dubois
Stephanie
S
Cencioni
Giulia
G
Marrocco
Jordan
J
Chouaib
Salem
S
Lemonnier
François A
FA
Jackson
Andrew Michael
AM
Kosmatopoulos
Kostas
K
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*
D019496:Cancer Vaccines; D000939:Epitopes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA