mRNA-4194

mRNA-4194 is an investigational mRNA-based cancer vaccine developed by Moderna in collaboration with the University of Oxford. It is specifically designed for the primary prevention of cancers in individuals with Lynch syndrome, a hereditary condition caused by germline mutations in DNA mismatch repair (MMR) genes. These mutations lead to microsatellite instability-high (MSI-H) status and the subsequent generation of shared frameshift neoantigens (FSNs) across various tumor types, most notably colorectal and endometrial cancers. mRNA-4194 encodes a selection of these shared FSNs and is encapsulated in lipid nanoparticles (LNPs) for delivery. The vaccine aims to stimulate a robust T-cell-mediated immune response that can recognize and eliminate precancerous cells expressing these neoantigens, thereby preventing the development of invasive malignancies. It is currently being evaluated in the Phase I/II INTERCEPT-Lynch trial, which focuses on healthy adults with Lynch syndrome who have no active cancer but are at high risk for MSI-H disease.