Triple negative breast cancer (TNBC) is the most aggressive sub-type of breast cancer, comprising approximately 20% of all breast cancers, and has a poor prognosis due to its aggressive behavior and lack of effective targeted therapies. In the present study, we employed transcriptome and protein analyses to select genes that are uniquely overexpressed in human triple-negative breast cancer. Overexpression of selected genes, Cyclin A2, CDK1, Cyclin E2, PRC1, Kif15, TPX2, Ki67, Top2A, were confirmed on human breast cancer tissue microarrays and in TNBC derived cell lines from C3(1)/TAg mice. Antigen-specific MHC class II epitopes with promiscuous high-binding affinity were identified using the “combined scoring system”, based on their potential to elicit a selective Th1 immunity. Furthermore, all peptides were selected to have over 85% amino acid sequence homology between human and mice for potential clinical translation. Strong immunogenic peptides from five antigens were selected by immunogenicity testing in tumor naïve mice based on high IFN-γ and low IL-10 ELISpot response data. The selected peptides, Cyclin A2 (#335), CDK1 (#113), Cyclin E2 (#93, 298, 334), KIF15 (#129), and Top2A (#236, 410, 606), were combined to form a multi-antigen, multi-peptide vaccine (MAMPV). The tumor preventive efficacy of the MAMPV was evaluated in syngraft study using a TNBC model: C3(1)/TAg-REAR mice and a TNBC cell line derived from C3(1)/TAg (M6). MAMPV-vaccinated animals demonstrated a significant reduction in tumor volume, and significantly higher tumor infiltration of CD4+ T cells compared to the control animals. Pathological examination of major organs did not reveal any toxicity associated with the vaccine. Similar tumor preventive efficacy was demonstrated in genetically engineered mouse model (GEMM) using C3(1)/TAg mice. Taken together, our data indicate that formulation of the multi-antigen multi-peptide vaccine is highly immunogenic and has the potential to be safe and efficacious in the immunoprevention of TNBC.

Citation Format: Yian Wang. Immunoprevention of triple negative breast cancer by a multi-antigen, multi-peptide vaccine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4563.