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

The T cell receptor (TCR) on CEA-specific CD8+ cytotoxic T lymphocytes is a specialized protein complex engineered or naturally occurring to recognize the carcinoembryonic antigen (CEA, also known as CEACAM5) when presented by Major Histocompatibility Complex (MHC) molecules (Parkhurst et al., 2011, Clinical Cancer Research). CEA is a cell surface glycoprotein highly expressed in various adenocarcinomas, particularly colorectal, pancreatic, and lung cancers, while having limited expression in normal adult tissues (Zhan et al., 2023, Frontiers in Immunology). When the CEA-specific TCR binds to its cognate CEA peptide-MHC complex, it triggers a signaling cascade within the CD8+ T cell, leading to the release of cytotoxic granules (perforin and granzymes) and pro-inflammatory cytokines that induce apoptosis in the target tumor cell (Holliger et al., 1999, Cancer Research). In the context of immunotherapy, patient T cells are often genetically modified to express these specific TCRs to enhance the immune system's ability to detect and eliminate CEA-positive malignancies (NCT01723306). However, therapeutic application faces challenges such as "on-target, off-tumor" toxicity due to low-level CEA expression in normal intestinal epithelium, which has been observed to cause severe colitis in clinical trials (Parkhurst et al., 2011).

Other names

CEA-specific T-cell receptorT-cell receptor specific for CEACAM5CEA-directed T-cell receptorCEA-specific TCR

The CEA-specific TCR recognizes the CEA peptide (e.g., CAP-1) presented by HLA-A*02:01 on the surface of tumor cells, triggering T-cell activation, cytokine production, and granzyme/perforin-mediated apoptosis of the target cell (Parkhurst et al., 2011; Zhan et al., 2023).