T cell receptor on cytotoxic T lymphocytes recognizing FGF-5 peptide–MHC complexes (FGF-5-specific TCR)

The T cell receptor (TCR) on cytotoxic T lymphocytes (CTLs) recognizing FGF-5 peptide–MHC complexes is a specialized immune receptor that mediates the recognition and destruction of cancer cells overexpressing Fibroblast Growth Factor 5 (FGF-5) (Hanada et al., 2001, PubMed: 11435298). FGF-5 is a non-mutated tumor-associated antigen (TAA) that is significantly upregulated in several human adenocarcinomas, most notably renal cell carcinoma (RCC), as well as prostate, breast, and pancreatic cancers (Hanada et al., 2001; Hanada et al., 2005, PubMed: 15897571). The TCR recognizes specific FGF-5-derived peptides, such as the HLA-A*0201-restricted decamer MLSVLEIFAV or the HLA-A*0301-restricted spliced peptide NTYASPRFK, when presented by Major Histocompatibility Complex (MHC) class I molecules on the tumor cell surface (ClinicalTrials.gov, NCT00089778; Gouttefangeas et al., 2007, PubMed: 17257361). Upon binding to these peptide-MHC (pMHC) complexes, the TCR initiates a signaling cascade that activates the CTL, resulting in the targeted lysis of the malignant cells through the secretion of cytotoxic granules (Molecular Biology of the Cell, 4th ed., NCBI). This target is being exploited in immunotherapy through the development of peptide vaccines and TCR-engineered T cell (TCR-T) therapies designed to stimulate or provide a robust anti-tumor immune response (NCI Drug Dictionary; Google Patents, US10639329B2). Clinical development has included trials of FGF-5 peptide vaccines combined with adjuvants like Montanide ISA-51 to treat patients with advanced renal cancer (NCT00089778).

Other names

FGF-5-specific T cell receptorTCR recognizing FGF-5/HLA-A2TCR recognizing FGF-5/HLA-A3FGF-5 peptide-MHC-specific TCRFibroblast growth factor 5-specific T cell receptor

The T cell receptor binds to specific FGF-5 peptides presented by HLA-A2 or HLA-A3 molecules on tumor cells, triggering a signaling cascade that activates cytotoxic T lymphocytes to release perforins and granzymes, leading to the targeted lysis of the cancer cells.