T-cell receptor specific for Folate Binding Protein peptide 191-199 (FBP191-199-specific TCR) (FBP191-199-specific TCR)

The T-cell receptor (TCR) specific for the Folate Binding Protein (FBP) peptide 191-199 is a specialized immune receptor designed to recognize a specific epitope of Folate Receptor alpha (FOLR1). FBP is a glycosylphosphatidylinositol-anchored glycoprotein that is highly overexpressed in various epithelial malignancies, particularly ovarian and breast cancers, while maintaining limited expression in normal tissues (Kim et al., 1999, J. Immunol). The FBP191-199 epitope, consisting of the amino acid sequence EQLYHSTMP, is an immunodominant peptide presented by the HLA-A*0201 molecule (Peoples et al., 1998, Clin. Cancer Res.). TCRs engineered to target this specific peptide-MHC complex enable CD8+ cytotoxic T cells to selectively identify and eliminate malignant cells, forming the basis for adoptive cell therapies like TCR-T (Knutson et al., 2006, J. Clin. Oncol.). This target is also utilized in peptide-based vaccines, such as E39, which aim to stimulate the endogenous production of these specific T cells to prevent cancer recurrence (Asher et al., 2020, J. Immunother. Cancer). Therapeutic challenges include overcoming the immunosuppressive tumor microenvironment and ensuring high specificity to avoid on-target off-tumor toxicities in healthy tissues expressing low levels of FBP.

Other names

Folate receptor alpha 191-199-specific TCREQLYHSTMP-specific T-cell receptorFOLR1-specific TCRFBP-specific TCRE39-specific TCR

The TCR specifically binds to the FBP191-199 peptide (EQLYHSTMP) presented by HLA-A*0201 molecules on the surface of tumor cells. This binding event triggers the formation of an immunological synapse, leading to the activation of downstream signaling pathways, the release of cytotoxic granules (perforin and granzymes), and the secretion of pro-inflammatory cytokines, ultimately resulting in the apoptosis of the target tumor cell (Kim et al., 1999, J. Immunol; Peoples et al., 1998, Clin. Cancer Res.).