Identification of peptide vaccine candidates sharing among HLA-A3+, -A11+, -A31+, and -A33+ cancer patients.

Abstract

PURPOSE:

Only a few studies have been reported on CTL epitope peptides restricted with alleles other than HLA-A2 and -A24. The HLA-A11, -A31, and -A33 alleles share similar binding motifs with HLA-A3 and -A68 alleles, and, thus, are classified as an HLA-A3 supertype. This study tried to identify CTL epitope peptides as vaccine candidates sharing by HLA-A3(+), -A11(+), -A31(+), and -A33(+) cancer patients.

EXPERIMENTAL DESIGN:

Seven peptides possessing the ability to induce HLA-A31-restricted and tumor-reactive CTLs were examined for their ability to induce HLA-A3-, -A11-, and -A33-restricted and tumor-reactive CTLs from peripheral blood mononuclear cells (PBMCs) of 18 epithelial cancer patients. The five reference peptides all have the ability to induce CTL activity restricted with one of the HLA-A3 supertypes, and, thus, were also examined as positive controls.

RESULTS:

Three peptides (2 from beta-tublin5- and 1 from CGI37-derived peptides) induced tumor-reactive CTLs in PBMCs of HLA-A3(+), -A11(+), and -A33(+) cancer patients with various frequencies (17-50%). One RLI- or KIAA0036-derived peptide induced tumor-reactive CTLs in PBMCs of HLA-A3(+) and -A11(+) or HLA-A11(+) and -A33(+) cancer patients also with various frequencies (22-67%), respectively, whereas the other peptide induced CTL activity in only HLA-A33(+) patients. Among the five reference peptides tested, one peptide, TRP2-197, induced CTL activity in both HLA-A11(+)- and -A33(+)-restricted manners.

CONCLUSIONS:

We identified new peptide vaccine candidates for HLA-A3, -A11, -A31, and -A33 positive cancer patients. This study may facilitate the development of both basic and clinical studies of peptide-based immunotherapy for cancer patients with other alleles of HLA-A2 and -A24.

• Authors: Hiroko Takedatsu, Shigeki Shichijo, Kazuko Katagiri, Hiromi Sawamizu, Michio Sata, Kyogo Itoh
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 3 Pg. 1112-20 (Feb 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 14871991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• DNA, Complementary
• Epitopes, T-Lymphocyte
• HLA-A Antigens
• HLA-A*33 antigen
• HLA-A11 Antigen
• HLA-A3 Antigen
• HLA-A31 antigen
• Peptides
• Vaccines, Subunit

Topics

• Alleles
• Animals
• CD8-Positive T-Lymphocytes (metabolism)
• COS Cells
• Cancer Vaccines
• Cell Line, Tumor
• Clinical Trials as Topic
• DNA, Complementary (metabolism)
• Dose-Response Relationship, Drug
• Epitopes, T-Lymphocyte (chemistry)
• HLA-A Antigens (biosynthesis)
• HLA-A11 Antigen
• HLA-A3 Antigen (biosynthesis)
• Humans
• Immunotherapy
• Leukocytes, Mononuclear (metabolism)
• Neoplasms (metabolism)
• Peptides (chemistry)
• Protein Binding
• Skin Neoplasms (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (metabolism)
• Vaccines, Subunit (chemistry)