Shared frameshift peptide neoantigens (209-FSP) (209-FSP)

The 209 shared frameshift peptide neoantigens are a specific set of tumor-specific antigens derived from mutations in microsatellite sequences within the coding regions of the genome. These mutations are a hallmark of tumors characterized by deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), which are frequently observed in colorectal, gastric, and endometrial cancers (Nouscom, 2024). Because these frameshift mutations are recurrent and shared across a high percentage of patients with these tumor types, they serve as ideal 'off-the-shelf' targets for immunotherapy. These peptides are processed by the tumor cells and presented on Major Histocompatibility Complex (MHC) molecules, where they are recognized as foreign by the immune system (D'Alise et al., 2022). Therapeutic strategies, most notably the NOUS-209 genetic vaccine, utilize these 209 antigens to prime and expand neoantigen-specific T cells. This approach aims to generate a robust and broad immune response that selectively destroys tumor cells while sparing healthy tissues, which do not harbor these specific frameshift mutations (NCT04041310).

Other names

Shared frameshift neoantigensMSI-H neoantigensNous-209 antigensFrameshift peptide neoantigensFSP-209

Induction of polyfunctional CD8+ and CD4+ T-cell responses against tumor cells that process and present these 209 shared frameshift peptides on MHC class I and II molecules (Nouscom, 2024; NCT04041310).