Carcinoembryonic antigen-derived peptide–Major Histocompatibility Complex-specific T-cell receptor (CEA-TCR)

The Carcinoembryonic antigen-derived peptide–Major Histocompatibility Complex-specific T-cell receptor (CEA-TCR) is an engineered or naturally occurring immune receptor designed to recognize specific peptide fragments of the Carcinoembryonic Antigen (CEA/CEACAM5) presented by MHC molecules, most commonly HLA-A*02:01. CEA is a cell-surface glycoprotein that is highly overexpressed in a wide range of adenocarcinomas, including colorectal, pancreatic, and lung cancers, making it a prominent target for adoptive T-cell therapy. In therapeutic contexts, patient T cells are genetically modified to express this TCR, allowing them to specifically target and lyse CEA-expressing tumor cells through the release of cytotoxic granules and cytokines. Clinical trials have demonstrated that CEA-TCR T cells can induce significant reductions in serum CEA levels and objective tumor regressions in patients with metastatic disease. However, a major therapeutic challenge is on-target off-tumor toxicity, as CEA is also expressed at lower levels in normal intestinal tissues, which has led to dose-limiting inflammatory colitis in some patients. Ongoing research focuses on enhancing the specificity and safety of these receptors through affinity tuning and the use of logic-gated systems to protect healthy tissues.

Other names

CEA-specific T-cell receptorAnti-CEA TCRCAP-1-specific TCRCEA:691-699-specific TCRCarcinoembryonic antigen-specific TCR

Recognition of CEA-derived peptides (such as CAP-1: YLSGANLNL) presented by HLA-A*02:01 on the surface of tumor cells, which triggers T-cell activation, the formation of an immunological synapse, and the release of cytotoxic granules (perforin and granzymes) and pro-inflammatory cytokines (e.g., IFN-gamma) to induce tumor cell lysis.