RNA-error derived neoantigen (RNA-neoantigen) (RNA-neoantigen)

RNA-error derived neoantigens are a novel class of tumor-specific antigens that arise from aberrations in RNA processing rather than somatic DNA mutations (Smart et al., 2018; Nature Biotechnology). These antigens are generated through mechanisms such as alternative splicing, intron retention, RNA editing, and the translation of non-coding regions or out-of-frame transcripts (Kahles et al., 2018; Cancer Cell; Zhang et al., 2018; Nature Communications). In many cancers, mutations in splicing factors like SF3B1 or the loss of RNA surveillance mechanisms lead to the production of these "non-genomic" peptides, which are subsequently presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Smith et al., 2019; Nature). Because these RNA-level errors are often shared across patients with similar molecular defects, they represent a significant opportunity for developing "off-the-shelf" immunotherapies in addition to personalized approaches (Frankiw et al., 2019; Nature Reviews Immunology). Therapeutic strategies targeting these neoantigens include personalized mRNA vaccines, peptide-based vaccines, and engineered TCR-T cell therapies designed to trigger a robust cytotoxic T-cell response against the tumor (CureVac, 2022). These targets are particularly valuable in "cold" tumors with low DNA mutational burdens but high rates of transcriptional or splicing dysregulation.

Other names

Non-genomic neoantigenSplicing-derived neoantigenTranscription-error derived neoantigenRNA-mediated neoantigenCryptic neoantigen

Induction of tumor-specific T-cell immunity by presenting non-self peptides derived from aberrant RNA processing (e.g., mis-splicing, RNA editing) on MHC molecules (Smart et al., 2018; Frankiw et al., 2019).