Moderna Merck intismeran meets phase 3 endpoints

Mutanome-guided immunopeptidomics of blood plasma for neoepitope detection in solid tumors is constrained by cfDNA variant calling sensitivity and MS detection limits

The study tests whether neoepitopes can be detected from blood plasma using mutanome-guided immunopeptidomics, a potential less invasive alternative to tissue biopsy. Wild-type immunopeptidomes from tissue and plasma overlapped by 58%, and 91% of plasma HLA ligands were rediscovered in tissue, but cfDNA-guided analysis identified no plasma neoepitopes. The authors attribute this to limited overlap between cfDNA and tumor genomic DNA mutanomes, reported at 15%, and mass-spectrometry detection limits. Using tumor genomic DNA as a complementary reference, two neoepitopes were detected in one patient, suggesting that liquid-biopsy neoantigen discovery remains constrained unless variant calling and MS sensitivity improve.