Abstract 4768: Investigation of frameshift peptides for cancer vaccines

Background: Our overall goal is to develop a general, preventative cancer vaccine. We are systematically applying bioinformatics, proteomics and immunological methods to achieve this vision. One of our foci is the identification of framshifted (FS) neo-peptides in tumor cells as vaccine components. FS peptides are expressed in alternate reading frames which are activated by various gene mutations and abnormal splicings in tumor cells. Aim/Method: Our hypothesis is that FS peptides are recognized as foreign antigens to the immune system thus making them potential cancer vaccine candidates. We have identified a list of FS peptides by bioinformatic analysis using the publically available human tumor and normal EST databases. To set up a systematical approach of prophylactic cancer vaccine development, we evaluated one potential FS peptide on the list as cancer vaccine candidate which is produced by a splice variant in SMC1A (Structural Maintenance of Chromosomes 1A). Results: The SMC1A FS peptide is a 17 amino acid peptide which is encoded by an abnormal alternative splicing event between exon 1 and exon 4. It was detected in mouse tumor cell lines including melanoma (n=2) and a breast tumor cell lines. It was also detected in human tumor cDNAs assayed thus far including breast (n=34), pancreas (n=4), and lung cancer (n=1) cell lines and primary breast (n=7) and pancreatic tumors (n=4). The expression levels of the SMC1 FS variant increases in most primary tumors with ranges from 2 to 70 fold. Specifically we see an increased expression in 6/7 breast and 2/4 pancreatic tumors screened. Single genetic immunization with plasmids expressing SMC1 FS, mouse GM-CSF, and CpG2216 significantly delayed tumor growth in C57BL/6 mice transplanted with the B16F10 melanoma cell line. Both antibody and IFN-γ released splenocytes to SMC1 FS were detected in immunized mice. Discussion: These findings suggest that the SMC1 FS peptide can be a potential cancer vaccine candidate to prevent various tumors. We are applying this same basic approach to accumulate sufficient antigens to constitute a broadly protective, prophylactic cancer vaccine. (This research is supported by an Innovation Award from the DoD and The Keck Foundation to SAJ.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4768.