Homma Shigenori, Harada Mamoru, Yano Hirohisa, Ogasawara Sachiko, Shichijo Shigeki, Matsueda Satoko, Komatsu Nobukazu, Shomura Hiroki, Maeda Yoshiaki, Sato Yuji, Todo Satoru, Itoh Kyogo
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Int J Oncol. 2006 Sep;29(3):577-87.
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.
鳞状细胞癌抗原（SCCA）是鳞状细胞癌的一种有用标志物。在本研究中，我们试图鉴定SCCA衍生肽，这些肽可应用于开发针对HLA - A24 +鳞状细胞癌或非鳞状细胞癌患者的特异性免疫疗法。使用定量PCR检测了多种鳞状细胞癌和非鳞状细胞癌系中SCCA mRNA的表达。通过免疫组织化学染色研究癌组织中SCCA蛋白的表达。此后，根据其与HLA - A24分子的结合基序制备了SCCA衍生肽候选物。在这些肽中，对那些经常被体液免疫识别的SCCA衍生肽，进一步测试它们从HLA - A24 +鳞状细胞癌或非鳞状细胞癌患者的外周血单个核细胞诱导癌反应性细胞毒性T淋巴细胞（CTL）的能力。结果，大多数鳞状细胞癌系和组织在mRNA和蛋白质水平上SCCA均呈阳性。相比之下，非鳞状细胞癌组织在蛋白质水平上几乎不表达，尽管腺癌细胞系在mRNA水平上部分表达。四种SCCA衍生肽经常被鳞状细胞癌和非鳞状细胞癌患者的免疫球蛋白G识别。在这些肽中，发现SCCA(112 - 120)和SCCA(215 - 224)肽均能有效地从鳞状细胞癌和非鳞状细胞癌患者的外周血单个核细胞诱导针对HLA - A24 + SCCA +癌细胞的肽特异性CTL。两种新鉴定的具有在鳞状细胞癌和非鳞状细胞癌患者中均诱导CTL活性能力的SCCA衍生肽，可能适用于HLA - A24 +鳞状细胞癌患者而非非鳞状细胞癌患者的特异性免疫疗法。
