Identification of squamous cell carcinoma antigen-derived peptides having the capacity of inducing cancer-reactive CTLs in HLA-A24+ cancer patients.
Squamous cell carcinoma antigen (SCCA) is a useful marker for SCCs. In this study, we attempted to identify SCCA-derived peptides that could be applied in the development of specific immunotherapy for HLA-A24+ cancer patients with SCC or non-SCC. A variety of SCC and non-SCC lines were examined for their expression of SCCA mRNA using quantitative PCR. SCCA protein expression in cancer tissues was investigated by immunohistochemical staining. Thereafter, SCCA-derived peptide candidates were prepared based on their binding motifs to HLA-A24 molecules. Among these peptides, SCCA-derived peptides that were frequently recognized by humoral immunity were further tested for their ability to induce cancer-reactive cytotoxic T lymphocytes (CTLs) from the peripheral blood mononuclear cells of HLA-A24+ patients with SCC or non-SCC. As a result, the majority of SCC lines and tissues were positive for SCCA both at mRNA and protein levels. By contrast, non-SCC cancer tissues hardly expressed it at the protein level, although adenocarcinoma cell lines partly expressed it at the mRNA level. Four SCCA-derived peptides were frequently recognized by immunoglobulin G of both SCC and non-SCC cancer patients. Among these peptides, both the SCCA(112-120) and SCCA(215-224) peptides were found to effectively induce peptide-specific CTLs toward HLA-A24+ SCCA+ cancer cells from the peripheral blood mononuclear cells of both SCC and non-SCC cancer patients. Two newly identified SCCA-derived peptides with the ability to induce CTL activity in both SCC and non-SCC cancer patients may be applicable to specific immunotherapy for HLA-A24+ cancer patients with SCC, but not those with non-SCC.
Homma
Shigenori
S
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Harada
Mamoru
M
Yano
Hirohisa
H
Ogasawara
Sachiko
S
Shichijo
Shigeki
S
Matsueda
Satoko
S
Komatsu
Nobukazu
N
Shomura
Hiroki
H
Maeda
Yoshiaki
Y
Sato
Yuji
Y
Todo
Satoru
S
Itoh
Kyogo
K
D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood; D009369:Neoplasms / Q000276:immunology*; D018307:Neoplasms, Squamous Cell / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D015843:Serpins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015843:Serpins; C051072:squamous cell carcinoma-related antigen