Transforming growth factor beta receptor type 2 frameshift neoantigen peptide-HLA complex (TGFBR2-fs neoantigen)

The Transforming growth factor beta receptor type 2 (TGFBR2) frameshift neoantigen is a tumor-specific antigen arising from a recurrent mutation in cancers characterized by microsatellite instability (MSI). In these tumors, a 1-base pair deletion within a poly-adenine (A10) tract of the TGFBR2 gene causes a frameshift, resulting in a truncated protein with a unique, non-self C-terminal peptide sequence (Saeterdal et al., 2001). This novel peptide is processed by the proteasome and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, most commonly HLA-A*02:01. Because this mutation is highly frequent in MSI-high colorectal, gastric, and endometrial cancers, it represents a shared neoantigen suitable for off-the-shelf immunotherapy (Linnebacher et al., 2001). Therapeutic approaches targeting this complex include cancer vaccines, such as Nous-209, and TCR-engineered T-cell therapies designed to recognize the specific peptide-HLA complex. These treatments aim to stimulate a robust cytotoxic T-lymphocyte response to selectively eliminate cancer cells while sparing normal tissues that lack the frameshift mutation.

Other names

TGFBR2 frameshift mutation neoantigenTGFBR2-fs peptideTGFBR2 (poly-A) frameshift neoantigenTGFBR2 mutation-derived antigenTGFBR2-fs-MHC complex

Induction of a specific cytotoxic T-lymphocyte (CTL) response against tumor cells presenting the frameshift-derived peptide on HLA molecules. Vaccines containing the neoantigen peptide stimulate the expansion of CD8+ and CD4+ T-cells that recognize the non-self C-terminal sequence generated by the TGFBR2 mutation (Saeterdal et al., 2001).