Identification of novel Lck-derived T helper epitope long peptides applicable for HLA-A2(+) cancer patients as cancer vaccine.
The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes (CTL) from Lck antigen (p56(Lck) ), the src family tyrosine kinase, which is known to be aberrantly expressed in metastatic cancers cells, in order to develop a long peptide-based cancer vaccine for HLA-A2(+) cancer patients. Based on the biding motif to the HLA-DR and HLA-A2 alleles, 94 peptides were prepared from the Lck antigen. These peptides were screened for their reactivity to immunoglobulin G (IgG) from plasma of cancer patients, followed by testing of their ability to induce both CD4(+) and CD8(+) T lymphocytes showing not only peptide-specific IFN-γ production but cytotoxicity against HLA-A2(+) cancer cells from peripheral blood mononuclear cells (PBMC) of HLA-A2(+) cancer patients. Among 94 peptides tested, the three T helper epitope long peptides and their inner CTL epitope short peptides with HLA-A2 binding motifs were frequently recognized by IgG of cancer patients, and efficiently induced both CD4(+) IFN-γ(+) and CD8(+) IFN-γ(+) T lymphocytes. Patients' PBMC stimulated with these long peptides showed cytotoxicity against HLA-A2(+) Lck(+) cancer cells in HLA-class I and HLA-class II dependent manners. These three peptides might be useful for long peptide-based vaccines for HLA-A2(+) cancer patients with Lck(+) tumor cells.
Cancer Vaccine Center, Kurume University, Kurume, Japan.
Satoko
S
Matsueda
Cancer Vaccine Center, Kurume University, Kurume, Japan.
Shigeki
S
Shichijo
Cancer Vaccine Center, Kurume University, Kurume, Japan.
Sayaka
S
Nagata
Cancer Vaccine Center, Kurume University, Kurume, Japan.
Chieko
C
Seki
Cancer Vaccine Development Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
Akira
A
Yamada
Cancer Vaccine Center, Kurume University, Kurume, Japan.|Clinical Research Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
Masanori
M
Noguchi
Cancer Vaccine Center, Kurume University, Kurume, Japan.
Kyogo
K
Itoh
D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010455:Peptides; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Antitumor effector cells and their induction; T lymphocyte epitopes; tumor antigens; tyrosin kinese p56(lck); vaccination therapy