Vaccine Targeted to Her-2 / ErbB2 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. [Cancer Res 2007;67(14):7028–36]