Tailored mRNA vaccines spark durable T cell immunity in adjuvant TNBC

A phase study in 14 women with adjuvant-treated triple-negative breast cancer shows individualized neoantigen mRNA–LPX vaccines encoding up to 20 mutations elicit robust, multi-epitope CD4+/CD8+ T cell responses that persist for years and correlate with relapse-free outcomes in most patients (up to ~6 years). Vaccinated T cells differentiate into cytotoxic, late-stage effector and stem-like memory (TSCM) phenotypes, with durable clonal lineages detected long after vaccination. Three relapses occurred due to weak responses, MHC I loss, or a genetically distinct recurrent tumor. The findings demonstrate the feasibility of on-demand personalized RNA vaccines and provide insights into immune escape and memory formation to guide future immunotherapy strategies.