RNA-error derived neoantigen frameshift peptide (REDN)

RNA-error derived neoantigen frameshift peptides (REDNs) are a novel class of tumor-specific antigens generated by errors in RNA processing, such as mis-splicing, exon skipping, and transcriptional insertions or deletions (1.2.1, 1.4.1). Unlike traditional neoantigens that stem from genomic DNA mutations, REDNs arise from the high error rates of transcription and splicing in cancer cells, which often overwhelm cellular quality control mechanisms like nonsense-mediated decay (1.1.1, 1.5.2). These errors result in frameshifts that produce entirely "non-self" peptide sequences, which are subsequently processed and presented on the cell surface by MHC Class I and Class II molecules (1.1.2, 1.3.2). Because these peptides are highly immunogenic and frequently shared across different patients or tumor types, they represent a potent target for "off-the-shelf" therapeutic and prophylactic cancer vaccines (1.2.4, 1.3.3). Current drug development efforts, such as the FAST (Frameshift Antigen Shared Therapy) platform, utilize these peptides to elicit robust T-cell and B-cell mediated immune responses against tumors (1.3.2, 1.3.3). Additionally, the presence of antibodies against these frameshift peptides in patient serum serves as a sensitive biomarker for early cancer detection and for predicting the efficacy of immune checkpoint inhibitors (1.2.2, 1.2.5).

Other names

RNA-error derived neoantigenFrameshift peptide (FSP)Frameshift neoantigen (FSNA)RNA-based frameshift variantMis-splicing derived neoantigenTranscriptional error-derived neoantigenRNA-error derived neoantigen (REDN)

Induction of tumor-specific T-cell and B-cell immune responses through the presentation of non-self frameshifted peptides on MHC Class I and II molecules.