Molecular and immunological evaluation of the transcription factor SOX-4 as a lung tumor vaccine antigen
Molecular and immunological evaluation of the transcription factor SOX-4 as a lung tumor vaccine antigen
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DOI：
10.4049/jimmunol.172.5.3319
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Kalos, M
中科院分区：
文献类型：
--
作者：
Friedman, RS;Bangur, CS;Kalos, M
发育转录因子SOX-4在原发性小细胞肺癌（SCLC）中高度和差异过表达。为了检验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。SOX-4 mRNA在这些肺肿瘤类型的很大一部分中被证明是过表达的。为了检验SOX-4的免疫潜力，我们评估了健康供者PBMC中SOX-4特异性CD4和CD8 T细胞的存在，以及SCLC患者血清中sox4特异性抗体的存在。我们在SCLC患者的血清中证实了CD4和CD8 T细胞的存在，这些细胞可以识别来自SOX-4的自然加工表位，以及SOX-4特异性抗体的存在，但在健康供者的血清中则不存在。针对SOX-4的肺肿瘤特异性过表达和全面ag特异性免疫反应的证明，支持将该分子用于开发基于全基因、肽或蛋白的肺癌疫苗接种策略。此外，从SOX-4中自然处理的T细胞和Ab表位的鉴定为开发基于多肽的肺癌疫苗接种策略以及监测接种过SOX-4的患者的特异性反应提供了有价值的工具。
The developmental transcription factor SOX-4 has been shown to he 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.