Vaccination with Human HER-2/neu(435-443) CTL Peptide Induces Effective Antitumor Immunity against HER-2/neu-Expressing Tumor CellsIn vivo
Copyright policy )Vaccination with Human HER-2/neu(435-443) CTL Peptide Induces Effective Antitumor Immunity against HER-2/neu-Expressing Tumor CellsIn vivo
AbstractHER-2/neu is a self-antigen expressed by tumors and nonmalignant epithelial tissues. The possibility of self-tolerance to HER-2/neu-derived epitopes has raised questions concerning their utility in antitumor immunotherapy. Altered HER-2/neu peptide ligands capable of eliciting enhanced immunity to tumor-associated HER-2/neu epitopes may circumvent this problem. The human CTL peptide HER-2/neu (435-443) [hHER-2(9435)] represents a xenogeneic altered peptide ligand of its mouse homologue, differing by one amino acid residue at position 4. In contrast to mHER-2(9435), vaccination of HLA-A*0201 transgenic (HHD) mice with hHER-2(9435) significantly increased the frequency of mHER-2(9435)-specific CTL and also induced strong protective and therapeutic immunity against the transplantable ALC tumor cell line transfected to coexpress HLA-A*0201 and hHER-2/neu or rHER-2/neu. Similar results were also obtained with wild-type C57BL/6 mice inoculated with HER-2/neu transfectants of ALC. Adoptive transfer of CD8+ CTL from mice immunized with hHER-2(9435) efficiently protected naive syngeneic mice inoculated with ALC tumors. In conclusion, our results show that HER-2(9435) serves as a tumor rejection molecule. They also propose a novel approach for generating enhanced immunity against a self-HER-2/neu CTL epitope by vaccinating with xenogeneic altered peptide ligands and provide useful insights for the design of improved peptide-based vaccines for the treatment of patients with HER-2/neu-overexpressing tumors. (Cancer Res 2006; 66(10): 5452-60)
- St Savas Hospital Greece
Mice, Knockout, Ovarian Neoplasms, HLA-A Antigens, Lymphoma, Receptor, ErbB-2, Epitopes, T-Lymphocyte, Granulocyte-Macrophage Colony-Stimulating Factor, Immunotherapy, Active, Mice, Transgenic, CD8-Positive T-Lymphocytes, Transfection, Peptide Fragments, Mice, Inbred C57BL, Mice, Cell Line, Tumor, HLA-A2 Antigen, Animals, Humans, Female, T-Lymphocytes, Cytotoxic
Mice, Knockout, Ovarian Neoplasms, HLA-A Antigens, Lymphoma, Receptor, ErbB-2, Epitopes, T-Lymphocyte, Granulocyte-Macrophage Colony-Stimulating Factor, Immunotherapy, Active, Mice, Transgenic, CD8-Positive T-Lymphocytes, Transfection, Peptide Fragments, Mice, Inbred C57BL, Mice, Cell Line, Tumor, HLA-A2 Antigen, Animals, Humans, Female, T-Lymphocytes, Cytotoxic
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