New peptide vaccine candidates for epithelial cancer patients with HLA-A3 supertype alleles.
We previously identified 2 cancer-associated antigens, immediate early response gene X-1 (IEX) and small GTPase (Ran), and their 5 epitopes using human leukocyte antigen (HLA)-A33-restricted and tumor-infiltrating T cells from a colon cancer patient. In this study, we examined whether or not these peptides can induce cytotoxic T lymphocytes (CTLs) in HLA-A11+ or HLA-A31+ epithelial cancer patients because the HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs as an HLA-A3 supertype family, which is widely distributed in many ethnic populations. Among them, the 2 peptides, IEX 47-56 and IEX 61-69, induced peptide-specific CTLs from peripheral blood mononuclear cells of cancer patients with the HLA-A11 and HLA-A31 alleles more efficiently than the other 3 peptides. Antibody blocking and cold inhibition experiments revealed that the cytotoxicity of peptide-induced CTLs against cancer cells was attributable to peptide-specific and CD8+ T cells. Together with our previous findings, these results indicate that the 2 IEX peptides could be appropriate vaccine candidates for HLA-A11, HLA-A31, and HLA-A33 positive epithelial cancer patients. This information could expand the chance of a peptide-based cancer vaccine for epithelial cancer patients of many ethnic populations.
Matsueda
Satoko
S
*Department of Immunology, Karume University School of Medicine, Karume, Fukuoka, Japan.
Takedatsu
Hiroko
H
Sasada
Tetsuro
T
Azuma
Koichi
K
Ishihara
Yuki
Y
Komohara
Yoshihiro
Y
Noguchi
Masanori
M
Shichijo
Shigeki
S
Itoh
Kyogo
K
Harada
Mamoru
M
D000483:Alleles; D019138:Antibodies, Blocking / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000473:pathology; D015234:HLA-A Antigens / Q000235:genetics; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology
D019138:Antibodies, Blocking; D051017:Apoptosis Regulatory Proteins; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen; C069527:HLA-A31 antigen; C099815:IER3 protein, human; D008565:Membrane Proteins; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D020931:ran GTP-Binding Protein