Toward the development of multi-epitope p53 cancer vaccines: an in vitro assessment of CD8(+) T cell responses to HLA class I-restricted wild-type sequence p53 peptides.
Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines. Six HLA-A2 or HLA-A24-restricted wt p53 peptides were evaluated for their ex vivo immunogenicity and their potential for use in cancer vaccines. Peripheral blood mononuclear cells (PBMC) obtained from HLA-A*0201(+) and/or HLA-A*2402(+) normal donors and subjects with squamous cell carcinoma of the head and neck (SCCHN) were analyzed for p53 peptide-specific reactivity in ELISPOT IFN-gamma assays. CD8(+) T cells in 7/10 normal donors (HD) and 11/23 subjects with SCCHN responded to at least one of the wt p53 peptides. CD8(+) T cell precursors responsive to wt p53 epitopes were detected in the circulation of most subjects with early disease, and an elevated blood Tc(1)/Tc(2) ratio distinguished wt p53 peptide responders from non-responders. The identification of multiple wt p53 peptides able to induce cytolytic T lymphocytes in most subjects with cancer promotes the development of multi-epitope p53 vaccines.
Sakakura
Koichi
K
Department of Otolaryngology, Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.
Chikamatsu
Kazuaki
K
Furuya
Nobuhiko
N
Appella
Ettore
E
Whiteside
Theresa L
TL
Deleo
Albert B
AB
D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53