New peptide vaccine candidates for epithelial cancer patients with HLA-A3 supertype alleles.

Abstract

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.

• Authors: Satoko Matsueda, Hiroko Takedatsu, Tetsuro Sasada, Koichi Azuma, Yuki Ishihara, Yoshihiro Komohara, Masanori Noguchi, Shigeki Shichijo, Kyogo Itoh, Mamoru Harada
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 30 Issue 3 Pg. 274-81 (Apr 2007) ISSN: 1524-9557 [Print] United States
• PMID: 17414318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Blocking
• Apoptosis Regulatory Proteins
• Cancer Vaccines
• HLA-A Antigens
• HLA-A11 Antigen
• HLA-A3 Antigen
• HLA-A31 antigen
• IER3 protein, human
• Membrane Proteins
• Peptide Fragments
• Vaccines, Subunit
• ran GTP-Binding Protein

Topics

• Alleles
• Antibodies, Blocking (pharmacology)
• Apoptosis Regulatory Proteins (chemistry, immunology, pharmacology)
• Cancer Vaccines (chemistry, immunology, pharmacology)
• Carcinoma (genetics, immunology)
• Epithelial Cells (pathology)
• HLA-A Antigens (genetics)
• HLA-A11 Antigen
• HLA-A3 Antigen (genetics)
• Humans
• Membrane Proteins (chemistry, immunology, pharmacology)
• Peptide Fragments (immunology, pharmacology)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Vaccines, Subunit (chemistry, immunology, pharmacology)
• ran GTP-Binding Protein (chemistry, immunology, pharmacology)