Abstract 1572: Development of novel and effective therapeutic peptide vaccines against HPV-induced tumors

Abstract

Abstract Our main goal is to generate effective therapeutic peptide-based vaccines against viral-induced cancers. We are first focusing on human papillomavirus (HPV) induced malignancies because of their high worldwide prevalence (e.g., cervical carcinoma and head & neck cancer). We have used an HPV-induced mouse cancer model to test vaccines composed of a CD8 T cell peptide epitope administered with potent adjuvants designed to generate vast numbers of high avidity cytotoxic T lymphocytes specific for the HPV16-E7 antigen. One vaccination strategy (TriVax) consists of intravenous administration of synthetic peptide HPV16-E749-57 administered together with a Poly-IC (a TLR3 agonist) and anti-CD40 monoclonal antibody (≥CD40 mAb) while the second more simple strategy (BiVax) comprises of peptide plus Poly-IC. We assessed both the immunogenicity and therapeutic anti-tumor effects of both vaccination strategies. While TriVax was clearly more immunogenic than BiVax, both vaccines showed remarkable anti tumor effects against the HPV16-E7 expressing tumors TC-1 and C3.43. In addition, we will present results suggesting that some peptides such as HPV16-E749-57 can be highly immunogenic in the absence of CD40 costimulation (i.e., in the BiVax format), due to their capacity to form complexes with Poly-IC. We hypothesize that peptide/Poly-IC complexes are highly immunogenic because they are targeted to professional antigen-presenting cells via some type of scavenger receptor specialized in capturing nucleic acids. 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 1572. doi:1538-7445.AM2012-1572