Brilliant epitopes for improved cancer vaccines

Project Summary We propose to advance next-generation cancer vaccines with superior immunogenic payloads for KRAS mutations, building upon the safety and proven efficacy of the mRNA-LNP platform for vaccine delivery. The totality of results from our proposal will advance preclinical optimization of a next-generation, lead vaccine, supporting IND submission and thoughtful advancement into clinical trials. We will focus on KRAS mutations because of their prevalence in pancreatic cancer, which is an indication with a poor prognosis with limited therapeutic modalities. We will characterize the immunogenicity of our novel vaccine products and evaluate the cross-reactivity of the T cell responses they prime that recognize tumor presented neoepitopes (Aim 1). We will perform this work by sequencing T cell receptors in mouse models containing humanized HLA alleles. Our approach has been enabled by the development of programmable mRNA vaccine platforms and new computational methods.