Frameshift peptide neoantigens (FSP neoantigens) (FSP)

Frameshift peptide (FSP) neoantigens are a class of tumor-specific antigens generated by frameshift mutations in coding microsatellites (cMS) or through errors in RNA transcription and splicing. These antigens are highly prevalent in cancers with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), such as those found in Lynch syndrome and approximately 15% of sporadic colorectal, gastric, and endometrial cancers. Specific genes frequently affected by these mutations include TAF1B, ASTE1 (also known as HT001), and TGFBR2, where the insertion or deletion of nucleotides creates a novel, highly immunogenic C-terminal peptide sequence. These peptides are processed and presented by Major Histocompatibility Complex (MHC) molecules on the cell surface, forming a unique MHC–peptide–TCR interface that can be recognized by T-cell receptors. Because these frameshift mutations are recurrent and shared across many patients with MSI-H tumors, they are ideal targets for 'off-the-shelf' cancer vaccines (e.g., Micoryx) and adoptive T-cell therapies (TCR-T). These therapies aim to stimulate a robust and durable immune response to eradicate tumor cells and potentially prevent cancer development in high-risk individuals.

Other names

Frameshift-derived neopeptides (FSDN)MSI-induced neoantigensCoding microsatellite (cMS) frameshift peptidesRNA-error derived neoantigensTAF1B/ASTE1/TGFBR2 frameshift peptides

Induction of a T-cell mediated immune response (specifically CD8+ cytotoxic and CD4+ helper T cells) against tumor cells presenting frameshift-derived peptides on their MHC molecules.