Transforming growth factor-beta receptor type 2 frameshift-mutated neoantigen (TGFBR2-FS)

The Transforming growth factor-beta receptor type 2 (TGFBR2) frameshift-mutated neoantigen is a tumor-specific peptide resulting from a common mutation in the TGFBR2 gene, specifically within a polyadenine (A10) tract in exon 3 (Saeterdal et al., 2001). This mutation is highly prevalent in cancers characterized by microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR), such as colorectal, gastric, and endometrial carcinomas (Tougeron et al., 2009). The frameshift leads to a premature stop codon and the production of a truncated protein with a novel, highly immunogenic C-terminal sequence that is not expressed in healthy cells (Linnebacher et al., 2001). Because this specific neoantigen is shared among a high percentage of MSI-H patients, it has become a primary target for "off-the-shelf" cancer immunotherapy, including viral-vectored vaccines like Nous-209 (D'Alise et al., 2022). These therapies work by stimulating the patient's immune system to generate neoantigen-specific T-cells that recognize and eliminate tumor cells presenting the mutated peptide on their surface (ClinicalTrials.gov, NCT04041310). This target is particularly significant for treating Lynch syndrome-associated cancers and sporadic MSI-H tumors that are often responsive to immune checkpoint inhibition (Mandal et al., 2019).

Other names

TGFBR2 frameshift peptideTGFBR2-fs neoantigenTGF-beta receptor type II frameshift mutationMSI-H TGFBR2 neoantigen

Active immunotherapy via induction of neoantigen-specific CD8+ and CD4+ T-cell responses to recognize and eliminate tumor cells expressing the frameshift-mutated TGFBR2 protein.