T-cell receptor recognizing frameshift peptide-MHC complexes (TCR-FSP-MHC)

The T-cell receptor (TCR) recognizing frameshift peptide (FSP)-MHC complexes is a specialized immune receptor found on the surface of CD8+ and CD4+ T lymphocytes. These receptors are specifically evolved or engineered to identify neoantigens generated by frameshift mutations, which are highly prevalent in cancers characterized by microsatellite instability (MSI) or deficient mismatch repair (dMMR). Because frameshift mutations create entirely new amino acid sequences not found in the normal human proteome, the resulting FSPs are highly immunogenic and perceived as foreign by the immune system. When these FSPs are processed and presented by Major Histocompatibility Complex (MHC) molecules, the specific TCR binds to the complex, triggering a robust immune response that includes the activation of cytotoxic CD8+ T cells and helper CD4+ T cells. In therapeutic oncology, this TCR-MHC interaction is the primary target for neoantigen vaccines like Nous-209, which aim to prime and expand these specific T-cell populations to treat MSI-H colorectal, gastric, and endometrial cancers. Additionally, engineered TCR-T cell therapies are being developed to provide patients with high-affinity receptors capable of recognizing these MSI-specific targets. The high specificity of this interaction for tumor-exclusive mutations minimizes the risk of off-target effects on healthy tissues, making it a cornerstone of precision immunotherapy.

Other names

Frameshift peptide-specific T-cell receptorMSI-specific T-cell receptorFSP-specific TCRNeoantigen-specific T-cell receptor

Induction and expansion of antigen-specific CD4+ and CD8+ T-cell populations that recognize frameshift neoantigens presented on MHC molecules to elicit targeted anti-tumor cytotoxicity.