Abstract 1196: Identification of lung cancer associated oncoantigens as targets for active immunotherapy

Abstract

Abstract Non small cell lung cancer (NSCLC) is the leading cause of cancer death in men and women. Therefore, the development of new therapeutic strategies is essential for improving the prognosis and treatment of patients. An interesting experimental model to study human lung adenocarcinoma is represented by p53R172HΔg/K-rasG12D mice. They develop aggressive NSCLC that metastasize to multiple sites and display a stepwise, directly age-related progression, mimicking several features observed in lung cancer patients. Lung cancer progression in p53R172HΔg/K-rasG12D mice was characterized by non-invasive magnetic resonance imaging (MRI), histopathological and immunohistochemical analysis. p53R172HΔg/K-rasG12D mice develop lung adenocarcinomas already evident in 10 week-old mice, with a variable degree of differentiation. A significant gender difference in tumor progression was observed, with females developing more tumors than males. Moreover, by using qRT-PCR, some of the antigens deregulated in human lung cancer turned out to be up-regulated also during cancer progression in our mouse model, suggesting that p53R172HΔg/K-rasG12D mice recapitulate the metastatic nature of human NSCLC. Identification of oncoantigens expressed during tumor development could provide an unprecedented opportunity to address the immune system against these molecules. RNA was extracted from lungs of 10, 20 and 30 week-old wild type (wt) and p53R172HΔg/K-rasG12D mice. Transcription profiling was done using Mouse Exon 1.0 ST arrays: we detected 282 genes significantly differentially expressed during different stages of cancer progression. Interestingly, some of the genes that were already deregulated in the early phases of the tumor development remained deregulated also in advanced stages, suggesting their possible application as early biomarkers or as vaccination targets. These genes were ranked to full-fill the minimal requirement for an oncoantigen; within the plasma membrane proteins we identified potential candidates: CXCR1, SLC16A6, SLC26A9 and ROS1. On the basis of the literature data and mouse data we consider ROS1 an interesting putative oncoantigen to be further investigated. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1196. doi:1538-7445.AM2012-1196