Friedman Rachel S, Bangur Chaitanya S, Zasloff Eden J, Fan Liqun, Wang Tongtong, Watanabe Yoshihiro, Kalos Michael
Corixa, Seattle, WA 98104, USA.
J Immunol. 2004 Mar 1;172(5):3319-27. doi: 10.4049/jimmunol.172.5.3319.
The developmental transcription factor SOX-4 has been shown to be highly and differentially overexpressed in primary small cell lung carcinomas (SCLC). To examine the potential of SOX-4 for broad use as a lung cancer vaccine, we have evaluated the expression of SOX-4 in a panel of primary adenocarcinoma, squamous, and large cell tumor samples as well as in a panel of established small cell and non-small cell lung carcinoma tumor cell lines. SOX-4 mRNA is shown to be overexpressed in a substantial fraction of each of these lung tumor types. To examine the immunological potential of SOX-4, we have evaluated the presence of SOX-4-specific CD4 and CD8 T cells in PBMC of healthy donors and the presence of SOX4-specific Abs in sera from SCLC patients. We demonstrate the presence of both CD4 and CD8 T cells that recognize naturally processed epitopes derived from SOX-4 as well as the presence of SOX-4-specific Abs in sera from SCLC patients, but not in sera from healthy donors. The lung tumor-specific overexpression and demonstration of a comprehensive Ag-specific immune response specific for SOX-4 support the use of this molecule in the development of whole gene-, peptide-, or protein-based vaccination strategies against lung cancer. Furthermore, the identification of naturally processed T cell and Ab epitopes from SOX-4 provides valuable tools for the development of peptide-based vaccination strategies against lung cancer as well as to monitor SOX-4-specific responses in vaccinated patients.
发育转录因子SOX-4已被证明在原发性小细胞肺癌（SCLC）中高度且差异表达。为了研究SOX-4作为肺癌疫苗广泛应用的潜力，我们评估了SOX-4在一组原发性腺癌、鳞状细胞癌和大细胞肿瘤样本以及一组已建立的小细胞和非小细胞肺癌肿瘤细胞系中的表达。结果显示，SOX-4 mRNA在这些肺癌类型中的很大一部分中均有过表达。为了研究SOX-4的免疫潜力，我们评估了健康供体外周血单核细胞（PBMC）中SOX-4特异性CD4和CD8 T细胞的存在情况以及SCLC患者血清中SOX4特异性抗体的存在情况。我们证明了存在能够识别源自SOX-4的天然加工表位的CD4和CD8 T细胞，以及SCLC患者血清中存在SOX-4特异性抗体，但健康供体血清中不存在。肺癌特异性过表达以及针对SOX-4的全面抗原特异性免疫反应的证明支持将该分子用于开发针对肺癌的全基因、肽或蛋白质疫苗接种策略。此外，从SOX-4中鉴定天然加工的T细胞和抗体表位为开发针对肺癌的肽疫苗接种策略以及监测接种患者中SOX-4特异性反应提供了有价值的工具。
