Abstract 647: Immunoprevention of triple negative breast cancer by a TOP2A multi-peptide vaccine

Abstract

Abstract Triple negative breast cancer (TNBC) comprises approximately 20% of all breast cancers, and it has a poor prognosis due to aggressive growth characteristics and lack of effective targeted therapies. Emerging data suggest vaccination as a promising approach to prevent TNBC as well as other cancer types, but appropriate vaccine targets need to be identified. In the present study, we employed in silico analyses to select genes that are uniquely expressed in TNBC. Topoisomerase 2 alpha (Top2A) was found to be highly expressed in human TNBC. Top2A is a key enzyme in DNA replication and has been identified as a target of anti-cancer therapy. Overexpression of Top2A was confirmed in human breast cancer tissue microarrays and in mouse TNBCs derived from C3(1)/TAg mice. Top2A-specific MHC class II epitopes with optimal binding affinity were identified using the “combined scoring system”, based on their potential to elicit a Th1 immune response. Furthermore, all peptides were selected to have 100% amino acid sequence homology between humans and mice for potential clinical translation. Four Top2A peptides with strong immunogenic responses were selected by immunization of tumor naïve mice followed by IFN-γ-based ELISPOT assays. These peptides were combined to form a multi-peptide Top2A vaccine. The anti-tumor efficacy of the Top2A vaccine was tested in a preventive setting using a syngeneic TNBC model in C3(1)/TAg-REAR mice. Vaccinated animals demonstrated a significant reduction in tumor growth when compared to the adjuvant control with tumor size decreasing from 278.1 mm3 in adjuvant control to 150.4 mm3 in vaccinated group (p < 0.05). Taken together, our data clearly demonstrate that the Top2A multi-peptide vaccine is highly immunogenic and provides immunopreventive efficacy against TNBC in mice. Citation Format: Sang Beom Lee, Jing Pan, Yueqiang Jiang, Katie Palen, Bryon Johnson, Romaine Ingrid Fernando, Shizuko Sei, Ronald Lubet, Ming You, Yian Wang. Immunoprevention of triple negative breast cancer by a TOP2A multi-peptide vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 647.