THAP domain-containing protein 2 frameshift neoantigen (THAP2-FS)

THAP domain-containing protein 2 (THAP2) frameshift neoantigen is a tumor-specific protein fragment generated by a frameshift mutation in the THAP2 gene, a phenomenon frequently observed in cancers characterized by microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) (PMID: 32699243). In these tumors, the failure of the DNA mismatch repair system leads to the expansion or contraction of short tandem repeats, such as the mononucleotide poly-A tract within the THAP2 coding sequence, resulting in a shift in the reading frame and the production of a novel C-terminal peptide (PMID: 30104718). This neoantigen is highly immunogenic because it lacks central tolerance, as the sequence is not present in the normal human proteome. THAP2 is considered a shared neoantigen because the same frameshift mutation occurs recurrently across different patients with MSI-H colorectal, gastric, and endometrial cancers (PMID: 33073218). This recurrence makes it an attractive target for off-the-shelf cancer immunotherapies, such as the Nous-209 genetic vaccine, which includes THAP2-FS in its multi-antigen payload to elicit robust CD8+ and CD4+ T-cell responses (NCT04041310). By targeting THAP2 and other shared neoantigens, these therapies aim to provide a broad and potent anti-tumor immune response specifically in the MSI-H patient population.

Other names

THAP2 frameshift mutationTHAP2-FS neoantigenTHAP2-derived frameshift peptideTHAP2-derived neoantigen

Induction of neoantigen-specific T-cell mediated cytotoxicity through viral vector-based vaccination.