T cell receptor recognizing CAP1-6D presented by HLA-A*02:01 (CAP1-6D-specific TCR)

The T cell receptor (TCR) recognizing the CAP1-6D peptide presented by HLA-A*02:01 is a specialized immune receptor utilized in the development of cancer immunotherapies, particularly TCR-engineered T-cell (TCR-T) therapies. CAP1-6D is a heteroclitic (modified) peptide derived from Carcinoembryonic Antigen (CEA), where an asparagine at position 6 is replaced by aspartic acid to increase its binding affinity for the HLA-A*02:01 molecule and enhance T-cell activation (Zaremba et al., 1997). CEA is a well-characterized tumor-associated antigen that is highly expressed in various epithelial malignancies, including colorectal, pancreatic, and lung cancers, while showing limited expression in normal adult tissues (Parkhurst et al., 2011). When expressed on the surface of cytotoxic T lymphocytes, this specific TCR enables the cells to recognize and bind to the CAP1-6D/HLA-A*02:01 complex on tumor cells. This interaction triggers a signaling cascade that leads to the release of cytotoxic granules, such as perforin and granzymes, resulting in the targeted destruction of the cancer cell. Clinical trials have explored the use of T cells transduced with this TCR to treat patients with metastatic colorectal cancer, though monitoring for gastrointestinal toxicity is critical due to low-level CEA expression in normal colonic mucosa (Parkhurst et al., 2011).

Other names

CEA-specific T-cell receptorHLA-A*02:01-restricted CEA TCRCAP1-6D TCRCarcinoembryonic antigen-specific T-cell receptor

The TCR specifically binds to the CAP1-6D peptide (an agonist variant of the CEA-derived CAP1 peptide) when presented by the HLA-A*02:01 MHC class I molecule. This binding event triggers the activation of the T cell, leading to the secretion of pro-inflammatory cytokines such as IFN-gamma and the directed release of cytotoxic granules containing perforin and granzymes to induce apoptosis in CEA-expressing tumor cells (Zaremba et al., 1997; Parkhurst et al., 2011).