IDENTIFICATION OF POTENTIAL HLA-A-ASTERISK-0201 RESTRICTED CTL EPITOPES DERIVED FROM THE EPITHELIAL-CELL ADHESION MOLECULE (EP-CAM) AND THECARCINOEMBRYONIC ANTIGEN (CEA)

The altered expression pattern of the Epithelial Cell Adhesion Molecul e (Ep-CAM) and the Carcinoembryonic Antigen (CEA) on tumor cells of ep ithelial origin as compared to normal epithelia may permit T cells to preferentially recognize and lyse these tumor cells. The binding affin ity for human leucocyte antigen A2.1 (HLA-A0201) and the capacity to form stable peptide-major histocompatibility complex (MHC) interaction s with this molecule were tested for 410 Ep-CAM-derived sequences, inc luding an overlapping set of 9 amino-acid-long peptides, and 73 CEA-de rived peptides fulfilling the HLA-A0201 motif. Peptides with a high b inding affinity and a low peptide-MHC dissociation rate were subsequen tly tested for their immunogenicity in HLA-A0201K(b) transgenic mice. One Ep-CAM-derived peptide and 1 CEA-derived peptide were able to rep roducibly induce peptide-specific cytotoxic T cells (CTL) in these mic e. This indicates that EpCAM and CEA are potential target antigens for CTL-mediated immunotherapy of epithelial cancers. (C) American Societ y for Histocompatibility and Immunogenetics, 1997.