Shared RNA error-derived frameshift neoantigen peptides (RNA-FS neoantigens)

Shared RNA error-derived frameshift neoantigen peptides represent a novel class of cancer targets arising from systematic errors in RNA transcription or splicing rather than traditional DNA mutations [1]. In canine oncology, these peptides are generated when the cellular machinery fails to accurately process mRNA, leading to out-of-frame translation and the production of novel, highly immunogenic amino acid sequences [3]. These neoantigens are subsequently processed and presented on the surface of tumor cells by the Major Histocompatibility Complex (MHC) Class I molecules, where they can be recognized by CD8+ T-cells [1]. Unlike traditional neoantigens which are often patient-specific, these RNA-derived frameshifts are frequently shared across different individuals and tumor types, making them ideal candidates for off-the-shelf cancer vaccines [1, 2]. Therapeutic strategies, such as those developed by Calviri, involve vaccinating dogs with a pool of these shared peptides to prime the immune system to recognize and destroy malignant cells [2]. This approach aims to provide broad protection against various cancers by targeting common biochemical failures inherent to the transformed state of tumor cells [3].

Other names

RNA-derived frameshift peptidesShared neoantigensFrameshift neoantigensFSNsSplicing-derived neoantigens

Induction of a cytotoxic T-lymphocyte (CTL) mediated immune response against tumor cells presenting shared frameshift peptides on MHC Class I molecules [1, 2].