Essential roles of tumor-derived helper T cell epitopes for an effective peptide-based tumor vaccine.
In this study, we identified a c-erbB-2/HER2/neu (HER2)-derived Th epitope (HER2 (16-30) ) and examined the role of Th epitopes in HER2-specific CD8+ T cell induction and in vivo tumor eradication, with a particular emphasis on the role of tumor cell-derived Th epitopes. Immunization of BALB/c mice using a mixture of Th epitope HER2 (16-30) and CTL epitope HER2 (63-71) administered subcutaneously with murine GM-CSF (mGM-CSF) induced a much higher level of HER2 (63-71) -specific CD8+ T cells compared with that obtained with the CTL epitope alone. HER2-unrelated OVA-derived Th epitope (OVA (323-339) ) exhibited a similar enhancing effect on HER2 (63-71) -specific CD8+ T cell induction. However, only mice immunized with HER2 (16-30) and HER2 (63-71), but not with a tumor-unrelated OVA (323-339) and HER2 (63-71), showed in vivo eradication of CMS5mHE tumor cells expressing HER2 but not OVA. This distinction was observed in preventative as well as therapeutic experimental settings. Conversely, both HER2 (16-30) and OVA (323-339) Th epitopes were equally effective in inducing the eradication of CMS5mHEOVA tumor cells which express HER2 as well as OVA. Our results clearly indicate that CTL and Th epitopes of target tumor cell origin should be used for effective induction of in vivo antitumor immunity.
Wang
Lijie
L
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, 514-8507, Japan.
Miyahara
Yoshihiro
Y
Kato
Takuma
T
Wang
Linan
L
Aota
Takumi
T
Kuribayashi
Kagemasa
K
Shiku
Hiroshi
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000008:administration & dosage* / Q000276:immunology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases