Human leukocyte antigen A*02:01 presenting modified Carcinoembryonic antigen peptide (HLA-A*02:01/CEA)

The HLA-A*02:01 presenting modified Carcinoembryonic antigen (CEA) peptide is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. CEA, also known as CEACAM5, is a cell-surface glycoprotein highly overexpressed in various adenocarcinomas, particularly colorectal, pancreatic, and lung cancers, while showing limited expression in normal adult tissues. The specific peptide often utilized is CAP1-6D (YLSGDNLNL), a modified version of the native CAP1 peptide (YLSGANLNL) where an aspartic acid substitution at the sixth position enhances binding affinity to the HLA-A*02:01 allele and increases immunogenicity. This complex serves as a highly specific anchor for T-cell receptors (TCRs), allowing for the development of TCR-based therapies such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers like ImmTACs. By targeting this pMHC, drugs can direct the immune system to selectively recognize and eliminate malignant cells that process and present CEA on their surface. Clinical development focuses on overcoming the immunosuppressive tumor microenvironment and managing potential on-target toxicities in the gastrointestinal tract.

Other names

HLA-A*02:01/CAP1-6DHLA-A2/CEA complexMHC-I/CEACAM5 peptide complexHLA-A*02:01-YLSGDNLNL complex

T-cell receptor (TCR) engagement leading to T-cell redirected killing of tumor cells expressing the specific peptide-MHC complex.