Carcinoembryonic antigen peptide CAP1-6D presented by HLA-A*02:01 (CAP1-6D/HLA-A2)

The CAP1-6D peptide presented by HLA-A*02:01 is a synthetic altered peptide ligand (APL) derived from the Carcinoembryonic Antigen (CEA), a cell surface glycoprotein highly expressed in various adenocarcinomas, particularly colorectal, pancreatic, and lung cancers [1][2]. The native CAP1 epitope (YLSGANLNL) is often poorly immunogenic; however, the CAP1-6D variant (YLSGADLNL) incorporates an asparagine-to-aspartic acid substitution at the sixth position, which significantly enhances its binding affinity to the T-cell receptor (TCR) and increases the potency of T-cell activation [1][3]. This peptide-MHC complex serves as a primary target for advanced immunotherapies, including TCR-engineered T cells and bispecific molecules like ImmTACs (e.g., IMC-C103C), which bridge T cells to tumor cells [4][5]. While CEA is a validated tumor-associated antigen, its low-level expression in normal gastrointestinal epithelium poses a risk for on-target, off-tumor toxicities such as inflammatory bowel-like symptoms [2][6]. Consequently, therapeutic development focusing on this target requires careful dose escalation and patient selection based on HLA-A*02:01 status and CEA expression levels [4][5].

Other names

CEA peptide CAP1-6DYLSGADLNL peptideHLA-A*02:01/CAP1-6D complexModified CEA peptide CAP1CAP1-6DCarcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) peptide CAP1-6D

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to the activation of cytotoxic T lymphocytes (CTLs) and subsequent lysis of CEA-expressing tumor cells.