T-cell receptor specific for Mucin-5AC peptide FLNDAGACV and HLA-A*0201 complex (MUC5AC-specific TCR)

T-cell receptors (TCRs) specific for the FLNDAGACV/HLA-A*0201 complex are specialized immune receptors that target a specific immunogenic epitope of Mucin-5AC (MUC5AC). MUC5AC is a high-molecular-weight, gel-forming glycoprotein that is typically absent in the normal pancreas but is highly overexpressed de novo in pancreatic ductal adenocarcinoma (PDAC) (PubMed: 21697763). The peptide FLNDAGACV, corresponding to residues 1398-1406 of MUC5AC, is a restricted epitope presented by the HLA-A*0201 MHC class I molecule on the surface of cancer cells (IEDB: 16385). Engineered T cells expressing these TCRs (TCR-T therapy) are being developed to provide a targeted immunotherapy for patients with advanced pancreatic cancer and other MUC5AC-expressing malignancies. While this approach offers high specificity for tumor cells, a significant therapeutic challenge is the potential for on-target off-tumor toxicity, as MUC5AC is also expressed in normal respiratory and gastric tissues (PubMed: 35625875). Monitoring for cytokine release syndrome and evaluating MUC5AC expression levels in patients are critical components of clinical development for this target.

Other names

T-cell receptor specific for FLNDAGACV/HLA-A*0201FLNDAGACV-specific TCRMUC5AC-A02-1398-specific TCRMUC5AC-specific T-cell receptor

The T-cell receptor (TCR) specifically recognizes and binds to the Mucin-5AC (MUC5AC) derived peptide FLNDAGACV when presented by the HLA-A*0201 major histocompatibility complex (MHC) class I molecule. This binding event triggers the activation of the T cell, leading to the release of cytotoxic granules such as perforin and granzymes, as well as pro-inflammatory cytokines like IFN-gamma, which results in the targeted lysis of MUC5AC-expressing tumor cells.