Abstract 3543: Combinatorial mRNA-LNP vaccines for triple-negative breast cancer

Abstract Breast cancer is the most commonly-diagnosed tumor in women, and there remains a need for effective treatment options for metastatic disease. mRNA-lipid nanoparticle (LNP) vaccines targeting tumor neoantigens are a potential avenue for treating triple-negative and basal-like breast cancers. Using established whole-exome and RNA-sequencing data, we identified a combination of neoantigens that induce CD4 and CD8 T cell responses. Administration of mRNA-LNPs encoding 4 neoantigens significantly delayed growth of 4T1 murine syngeneic tumors. When the vaccine is combined with IV injection of engineered IL7 and IL12, the median overall survival is increased by 14 days. Taken together, these improvements to current breast cancer vaccination approaches may represent a way to induce tumor regression and clearance in treatment-refractory disease. Citation Format: Sara L. Woessner, Xiaolei Cai, Caroline Kellogg, Jun Huang. Combinatorial mRNA-LNP vaccines for triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3543.