RNA error-derived tumor neoantigens (REDN)

RNA error-derived tumor neoantigens (REDNs) are a novel class of tumor-specific antigens generated by inaccuracies in RNA processing, such as transcription slippage at microsatellites, mis-splicing, and aberrant RNA editing (Shen et al., 2019). These errors result in the production of frameshift peptides (FSPs) that are absent in normal tissues and are subsequently processed and presented on the Major Histocompatibility Complex (MHC) of tumor cells (Calviri, 2024). In hemangiosarcoma, a highly aggressive cancer of the blood vessels, these neoantigens serve as potent targets for immunotherapy because they are often shared across different individuals and tumor types (Anticancer Drugs, 2024). Unlike traditional neoantigens derived from unique DNA mutations, REDNs allow for the development of "off-the-shelf" vaccines that can be administered to a broad population. Therapeutic vaccines targeting these neoantigens, such as those currently in clinical trials for canine hemangiosarcoma, aim to prime the immune system to recognize and eliminate malignant cells (Calviri, 2024). The Scout Out Canine Hemangiosarcoma (SOCH) trial is currently evaluating the efficacy of a pre-made REDN vaccine in dogs with early-stage disease to extend survival (Calviri, 2024). By inducing a T-cell response against these shared variants, the vaccine aims to overcome the limitations of low mutational burden in certain tumors (Anticancer Drugs, 2024). Preliminary results from large-scale canine studies suggest that these vaccines are safe and do not induce significant adverse effects (Calviri, 2024). This approach represents a significant shift in oncology, moving from personalized treatments to broadly applicable immunotherapies based on shared RNA-level defects. Overall, REDNs represent a promising frontier for both the prevention and treatment of aggressive cancers like hemangiosarcoma.

Other names

RNA-error derived neoantigensREDNsFrameshift peptidesFSPsRNA editing-derived neoantigensRED-neoantigensRNA-derived neoepitopes

Vaccination with shared RNA error-derived neoantigens stimulates the production of neoantigen-specific T cells (CD4+ and CD8+) that recognize and lyse tumor cells presenting these peptides on their surface MHC molecules.