Transforming growth factor beta receptor type 2 (TGFBR2) frameshift-mutant-derived neoepitope (TGFBR2-fs neoepitope)

The Transforming growth factor beta receptor type 2 (TGFBR2) frameshift-mutant-derived neoepitope is a tumor-specific antigen resulting from a common frameshift mutation in the TGFBR2 gene (PubMed: 10348378). This mutation typically occurs in a polyadenine (A10) tract within exon 3 and is highly prevalent in cancers characterized by microsatellite instability (MSI), such as colorectal and gastric cancers (PubMed: 28934463). The frameshift generates a novel, non-self amino acid sequence at the C-terminus of the truncated protein, which can be processed and presented by Major Histocompatibility Complex (MHC) molecules (PubMed: 33024317). Because this sequence is entirely absent from the normal human proteome, it serves as an ideal target for immunotherapy with minimal risk of cross-reactivity with healthy tissues. Therapeutic strategies targeting this neoepitope include cancer vaccines like Nous-209 and adoptive T-cell therapies designed to stimulate a robust cytotoxic T-lymphocyte response against MSI-high tumor cells (ClinicalTrials.gov: NCT04041310). Clinical development is currently focused on using these neoepitopes to treat patients with Lynch syndrome or sporadic MSI-H malignancies. By eliciting a targeted immune response, these therapies aim to eliminate tumor cells while sparing normal cells that lack the mutation.

Other names

TGFBR2 frameshift neoantigenTGFBR2-fs peptideTGFBR2 exon 3 frameshift mutationTGFBR2 -1bp frameshift neoepitopeTGFBR2 poly-A tract frameshiftTGFBR2-fs

Induction of tumor-specific T-cell responses against cells expressing the frameshift-mutated TGFBR2 protein.