Abstract 1570: Frameshift peptides as prophylactic cancer vaccines antigens

Abstract

Abstract Background: The goal of the project is to develop a universal, prophylactic cancer vaccine. We are integrating bioinformatics, genetics, proteomics and immunological methods to identify tumor DNA-encoded components for the development of an effective vaccine. In a previous study, we used bioinformatic and genetics analyses to identify a list of abberant transcripts associated with tumor cells that encode frameshift-derived (FS) neo-peptides. These FS peptides are a result of various gene mutations and abnormal splicings in tumor cells that would cause expression of gene sequences in alternate reading frames. The transcript encoding one of these vaccine component candidates, SMC1A (Structural Maintenance of Chromosomes 1A) FS was detected in numerous mouse and human tumor cell lines and primary human breast and pancreatic tumors. One dose genetic immunization with a plasmid expressing SMC1A FS significantly delayed tumor growth in C57BL/6 mice transplanted with the B16F10 melanoma cell line. To exam protection of SMC1A FS in a more realistic prophylactic model, we investigated the protection of SMC1A FS in two mouse spontaneous breast tumor models. Results: We similarly detected the transcript corresponding to the SMC1A FS peptide in tumors from spontaneous mouse breast tumor models: FVB/N-NeuT and BALB-NeuT. The SMC1A FS expression increases with the expression of Rat Her-2 in mouse mammary gland. Wild type and mutated Rat Her 2 are the oncogenes that induce spontaneously breast tumor development in FVB/N-NeuT and BALB-NeuT respectively. Both anti-SMC1A FS IgG and SMC1A FS peptide induced IFN-γ released splenocytes were detected in non-treated tumor bearing FVB/N-NeuT mice. One dose genetic immunization of mice with an SMC1A FS expression plasmid significantly reduced spontaneous breast tumor development in FVB/N-NeuT mouse as compared to that in non-treated mice. Genetic immunization followed by a protein boost (prime/boost regimen) in BALB-NeuT mice also significantly reduced tumor development and the reduction is associated with antibody reactivity to SMC1A FS. Discussion: The protection of SMC1A FS prophylactic immunization in spontaneous mouse tumor models indicates SMC1A S can be a potential prophylactic cancer vaccine candidate to prevent a variety of tumors types. We are applying the 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 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 1570. doi:1538-7445.AM2012-1570