Transforming growth factor beta receptor 2 frameshift neoantigen (TGFBR2-fs)

The Transforming growth factor beta receptor 2 (TGFBR2) frameshift neoantigen is a tumor-specific antigen resulting from a common somatic mutation in cancers with microsatellite instability (MSI). In MSI-high (MSI-H) tumors, such as colorectal and gastric cancers, the loss of DNA mismatch repair activity frequently leads to a 1-base pair deletion within a polyadenine (A10) tract in exon 3 of the TGFBR2 gene. This frameshift mutation generates a novel, highly immunogenic C-terminal peptide sequence that is not present in normal human tissues. Because this specific neoantigen is shared across a high percentage of MSI-H patients—occurring in approximately 90% of MSI-H colorectal cancers—it is considered a 'public' neoantigen and an ideal target for cancer vaccines. Therapeutic strategies involve using synthetic peptides or viral vectors to prime the immune system to recognize and eliminate cells presenting this frameshift peptide on their surface. Clinical development is currently focused on multi-antigen vaccines that include TGFBR2-fs to treat patients with dMMR/MSI-H solid tumors, often in combination with immune checkpoint inhibitors.

Other names

TGFBR2 frameshift peptideTGFBR2 mutation-derived neoantigenTGFBR2-fsTGF-beta receptor type II frameshift mutation

Active immunotherapy via vaccination to induce CD8+ and CD4+ T-cell mediated lysis of tumor cells expressing the frameshift-derived peptide.