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

The Transforming growth factor beta receptor type 2 (TGFBR2) frameshift mutant neoantigen peptide is a highly specific tumor antigen generated by a common mutation in cancers with microsatellite instability (MSI-H) (Markowitz et al., 1995). In these tumors, a deletion within a polyadenine (A10) tract of the TGFBR2 gene causes a frameshift, resulting in a novel, non-self peptide sequence that is not present in healthy tissues (Saeterdal et al., 2001). This neoantigen is processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, most notably HLA-A*02:01. Because this mutation is a frequent 'driver' event in MSI-H colorectal, gastric, and endometrial cancers, it serves as an ideal target for immunotherapy. Therapeutic strategies include neoantigen-based vaccines, such as Nous-209, and T-cell receptor (TCR) engineered T-cell therapies designed to recognize the peptide-HLA complex (NCT04041310). These treatments aim to stimulate the immune system to selectively identify and destroy malignant cells while sparing normal cells that lack the mutation. The high prevalence of this specific frameshift across different patients makes it a rare example of a 'shared' neoantigen, facilitating the development of off-the-shelf immunotherapies.

Other names

TGFBR2 frameshift peptideTGFBR2-fsTGFBR2 mutation-derived neoantigenTGFBR2 (131-159) frameshift peptideTGFBR2-fs-MHC complex

Induction of antigen-specific cytotoxic T-lymphocyte (CTL) responses through T-cell receptor (TCR) recognition of the peptide-HLA complex, leading to the selective lysis of tumor cells expressing the frameshift mutation (Linnebacher et al., 2001).