Large-scale transcript variants dictate neoepitopes for cancer immunotherapy.

ABSTRACT: Precise neoepitope discovery is crucial for effective cancer therapeutic vaccines. Conventional approaches struggle to build a repertoire with sufficient immunogenic epitopes. We developed a workflow leveraging full-length ribosome-nascent chain complex-bound mRNA sequencing (FL-RNC seq) and artificial intelligence-based predictive models to accurately identify the neoepitope landscape, especially large-scale transcript variants (LSTVs) missed by short-read sequencing. In the MC38 mouse model, we identified 22 LSTV-derived neoepitopes encoded by a synthesized mRNA lipid nanoparticle vaccine. As a standalone therapy and combined with anti-PD-1 immunotherapy, the vaccine curbed tumor progression, induced robust T cell-specific immunity, and modulated the tumor microenvironment. This undersco

SUBMITTER: Ji S 

PROVIDER: S-EPMC11784853 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature