Carcinoembryonic antigen-HLA-A*02:01 complex (CEA-HLA-A2)

The Carcinoembryonic antigen-HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various adenocarcinoma cells (UniProt P06731). It consists of a processed peptide fragment from the Carcinoembryonic Antigen (CEA/CEACAM5), such as the immunodominant CAP-1 peptide (YLSGANLNL), bound within the groove of the Human Leukocyte Antigen A*02:01 molecule (PubMed: 7543510). While CEA is a well-known tumor-associated antigen overexpressed in colorectal, pancreatic, and lung cancers, its presentation via HLA-A2 allows for highly specific targeting by T-cell-based immunotherapies. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers like IMC-C103C, which bypass the need for natural T-cell priming (Immunocore, 2023). These drugs aim to redirect the immune system to recognize and eliminate malignant cells expressing the complex. However, because CEA is also expressed at lower levels in normal gastrointestinal epithelium, safety monitoring for on-target off-tumor effects is critical during clinical development (PubMed: 15501977).

Other names

CEACAM5-HLA-A*02:01CEA peptide-MHC complexCAP-1-HLA-A2 complexCarcinoembryonic antigen-related cell adhesion molecule 5-HLA-A2 complex

T-cell receptor (TCR) mediated recognition leading to T-cell activation and cytotoxic lysis of tumor cells.