Human Leukocyte Antigen A*02:01 presenting Carcinoembryonic Antigen peptide CAP1-6D (HLA-A*02:01/CAP1-6D)

The HLA-A2 presenting CAP1-6D peptide is a peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapies. It comprises the Human Leukocyte Antigen A*02:01 molecule presenting a modified 9-amino acid epitope (YLSGADLNL) derived from Carcinoembryonic Antigen (CEA), a glycoprotein overexpressed in over 90% of colorectal cancers as well as pancreatic and gastric malignancies (Zaremba et al., 1997, Cancer Research). The CAP1-6D peptide is an agonist or heteroclitic peptide, where a substitution of aspartic acid for asparagine at the sixth position enhances its binding affinity to the T-cell receptor (TCR). This modification leads to more potent activation of cytotoxic T-lymphocytes compared to the native sequence (Fong et al., 2001, PNAS). This complex is targeted by various therapeutic modalities, including viral vector vaccines like CEA-TRICOM and TCR-engineered T-cell therapies, which aim to redirect the immune system to recognize CEA-positive tumor cells (Marshall et al., 2005, Journal of Clinical Oncology). Clinical use of this target requires patient screening for the HLA-A*02:01 genotype and CEA tumor expression. Potential safety concerns include on-target, off-tumor reactivity against normal tissues expressing low levels of CEA, such as the gastrointestinal epithelium.

Other names

HLA-A2/CEA(6D)CEA CAP1-6DYLSGADLNL-HLA-A*02:01 complexCarcinoembryonic antigen peptide 1-6DCEA agonist peptide CAP1-6D

Induction of a cytotoxic T-lymphocyte response through the specific recognition of the peptide-MHC complex by T-cell receptors.