Caspase-5 frameshift-derived peptide (CASP5 FSP)

Caspase-5 (CASP5) frameshift-derived peptides are neoantigens produced by somatic mutations in the CASP5 gene, which are frequently observed in tumors with microsatellite instability (MSI), such as colorectal, gastric, and endometrial cancers (PMID: 10508494). These mutations typically involve the deletion or insertion of nucleotides in a mononucleotide (A)10 repeat, leading to a shift in the reading frame and the production of a novel, highly immunogenic C-terminal peptide sequence (PMID: 32690471). Because these peptides are absent in normal tissues, they serve as ideal targets for immunotherapy, particularly cancer vaccines designed to stimulate a T-cell-mediated anti-tumor response. Therapeutic candidates like the Nous-209 vaccine incorporate these shared frameshift neoantigens to treat patients with MSI-high (MSI-H) or mismatch repair-deficient (dMMR) tumors (NCT04041310). By targeting these specific mutations, clinicians can induce a robust and specific immune response while minimizing off-target effects on healthy cells. This approach leverages the high mutational burden of MSI-H cancers to create "off-the-shelf" personalized therapies.

Other names

Caspase-5 neoantigenCASP5 frameshift mutation-derived peptideMSI-associated CASP5 peptide

Vaccine-mediated induction of CD8+ and CD4+ T-cell responses against frameshift neoantigens expressed on the surface of tumor cells.