Carcinoembryonic antigen-related cell adhesion molecule 5-derived HLA-A*02:01-restricted epitope (CEACAM5 HLA-A2 epitope)

The CEACAM5-derived HLA-A2-restricted epitope is a specific peptide fragment, most notably the CAP-1 peptide (YLSGANLNL), derived from the Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and presented by the Human Leukocyte Antigen A*02:01 (HLA-A2) molecule (Tsang et al., 1995, JNCI). CEACAM5 is a cell surface glycoprotein involved in cell adhesion and is highly overexpressed in various adenocarcinomas, particularly colorectal, pancreatic, and lung cancers (Kawashima et al., 1999, Cancer Research). While the full-length protein is a target for antibody-drug conjugates and bispecific antibodies, the HLA-A2-restricted epitope serves as a precise target for T-cell receptor (TCR)-based therapies, including TCR-engineered T cells (TCR-T) and peptide vaccines (NIH, ClinicalTrials.gov). These therapies aim to leverage the cellular immune system to recognize and eliminate cancer cells presenting the CEA peptide on their surface. Because CEACAM5 is also expressed at lower levels in normal mucosal tissues, therapeutic development must carefully manage potential on-target, off-tumor toxicities such as inflammatory responses in the gastrointestinal tract. Clinical monitoring often involves screening patients for the HLA-A*02:01 allele and high CEACAM5 expression to ensure target availability and therapeutic efficacy.

Other names

CEA-derived HLA-A2-restricted epitopeCAP-1 peptideYLSGANLNLCarcinoembryonic antigen peptide-1CEA HLA-A2 pMHCCEACAM5-derived peptide-MHC complex

T-cell receptor (TCR) binding to the peptide-MHC complex on the tumor cell surface, leading to CD8+ T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and targeted tumor cell lysis.