RNA-error derived neoantigens (REDNs) (REDNs)

RNA-error derived neoantigens (REDNs) are a novel class of tumor-specific antigens that arise from errors in RNA synthesis and processing, such as transcription slips, mis-splicing, and frameshifts, rather than somatic DNA mutations (11, 12). In canine hemangiosarcoma (HSA) and other malignancies, these RNA-level mistakes occur at a significantly higher frequency than DNA mutations, leading to the production of highly immunogenic frameshift peptides (9, 10). A defining characteristic of REDNs is that they are frequently shared across different individuals and tumor types, which contrasts with the highly personalized nature of traditional DNA-derived neoantigens (2, 6). This shared nature enables the development of "off-the-shelf" therapeutic and preventative vaccines, such as those currently being evaluated in the SOCH and VACCS clinical trials for dogs (3, 4). These vaccines aim to prime the immune system to recognize and eliminate early-stage cancer cells by stimulating both T-cell and antibody-mediated responses (5, 11). Additionally, the presence of circulating antibodies against these neoantigens serves as a sensitive biomarker for early cancer detection through specialized diagnostic assays (8, 13).

Other names

RNA-error derived neoantigensREDNsFrameshift neoantigensRNA-derived neoantigensShared frameshift peptidesRNA-error derived shared neoantigens

Induction of T-cell and B-cell mediated immune responses against shared frameshift peptides derived from RNA processing errors in tumor cells.