Calogero Raffaele Adolfo, Quaglino Elena, Saviozzi Silvia, Forni Guido, Cavallo Federica
Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin, Italy.
Cancer Immunol Immunother. 2008 Nov;57(11):1685-94. doi: 10.1007/s00262-008-0481-x. Epub 2008 Feb 20.
Neoplastic transformation is a multistage process and distinct gene products of specific cell regulatory pathways are involved at each stage. Identification of genes overexpressed at a specific stage provides an unprecedented opportunity to address the immune system against antigens with a driving role in tumor progression (oncoantigens). The ERBB2 oncogene is a prototype of deregulated oncogenic protein kinase membrane receptors. Mice transgenic for rat ERBB2 (BALB-neuT mice) were used in this study to identify an additional set of oncoantigens expressed at defined stages by most breast carcinomas to be used as alternatives to ERBB2-driven vaccination. To address this question, we integrated the transcription data generated by comparing preneoplastic lesions and neoplasia in BALB-neuT mice with a meta-analysis on transcription profiles generated from normal and breast tumor human specimens. Forty-six putative oncoantigens identified and prioritized according to their expression on the cell membrane or in the extra cellular space, cytoplasm and nucleus were chosen for preclinical investigation as vaccination targets.
肿瘤转化是一个多阶段过程,特定细胞调节途径的不同基因产物在每个阶段都发挥作用。鉴定在特定阶段过度表达的基因,为针对在肿瘤进展中起驱动作用的抗原(癌抗原)的免疫系统提供了前所未有的机遇。ERBB2癌基因是失调的致癌蛋白激酶膜受体的一个原型。本研究使用了转大鼠ERBB2基因的小鼠(BALB-neuT小鼠),以鉴定大多数乳腺癌在特定阶段表达的另一组癌抗原,用作ERBB2驱动疫苗接种的替代方案。为解决这个问题,我们将比较BALB-neuT小鼠的癌前病变和肿瘤形成所产生的转录数据,与对来自正常和乳腺肿瘤人类标本的转录谱进行的荟萃分析相结合。根据其在细胞膜、细胞外空间、细胞质和细胞核中的表达鉴定并排序的46种假定癌抗原,被选为疫苗接种靶点进行临床前研究。