Carcinoembryonic antigen-specific T-cell receptor (CEA-TCR) (CEA-TCR)

The Carcinoembryonic antigen-specific T-cell receptor (CEA-TCR) is an engineered immune receptor designed to recognize peptide fragments of the Carcinoembryonic Antigen (CEA, also known as CEACAM5) when presented by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (Parkhurst et al., 2011). CEA is a cell-surface glycoprotein that is highly overexpressed in various epithelial malignancies, including colorectal, pancreatic, and gastric cancers, while its expression in healthy adults is primarily limited to the gastrointestinal epithelium (UniProt P06731). In adoptive cell therapy, patient-derived T-cells are genetically modified to express these specific TCRs, enabling the immune system to target and eliminate CEA-positive tumor cells. While these therapies have demonstrated the potential for objective clinical responses in patients with metastatic disease, they are associated with significant safety challenges. Specifically, 'on-target, off-tumor' toxicity can occur because the TCRs also recognize the low levels of CEA present in normal colonic tissue, which has historically led to severe, dose-limiting inflammatory colitis in clinical trials (Thistlethwaite et al., 2017). Consequently, current research focuses on optimizing TCR affinity and incorporating safety switches to improve the therapeutic window and minimize adverse effects like cytokine release syndrome.

Other names

CEACAM5-specific T-cell receptorAnti-CEA TCRCEA-directed T-cell receptorT-cell receptor specific for CEA-derived peptides

Engineered T-cells expressing the CEA-specific TCR recognize CEA-derived peptides presented by HLA-A*02:01 on tumor cells, triggering T-cell activation and tumor cell lysis.