Identification of potential HLA-A *0201 restricted CTL epitopes derived from the epithelial cell adhesion molecule (Ep-CAM) and the carcinoembryonic antigen (CEA).
The altered expression pattern of the Epithelial Cell Adhesion Molecule (Ep-CAM) and the Carcinoembryonic Antigen (CEA) on tumor cells of epithelial origin as compared to normal epithelia may permit T cells to preferentially recognize and lyse these tumor cells. The binding affinity for human leucocyte antigen A2.1 (HLA-A*0201) and the capacity to form stable peptide-major histocompatibility complex (MHC) interactions with this molecule were tested for 410 Ep-CAM-derived sequences, including an overlapping set of 9 amino-acid-long peptides, and 73 CEA-derived peptides fulfilling the HLA-A*0201 motif. Peptides with a high binding affinity and a low peptide-MHC dissociation rate were subsequently tested for their immunogenicity in HLA-A*0201Kb transgenic mice. One Ep-CAM-derived peptide and 1 CEA-derived peptide were able to reproducibly induce peptide-specific cytotoxic T cells (CTL) in these mice. This indicates that EpCAM and CEA are potential target antigens for CTL-mediated immunotherapy of epithelial cancers.
Ras
E
E
Department of Immunohaematology and Blood Bank, University Hospital Leiden, The Netherlands.
van der Burg
S H
SH
Zegveld
S T
ST
Brandt
R M
RM
Kuppen
P J
PJ
Offringa
R
R
Warnarr
S O
SO
van de Velde
C J
CJ
Melief
C J
CJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D000071858:Epithelial Cell Adhesion Molecule; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000235:genetics
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D000939:Epitopes; D015789:HLA-A2 Antigen; D010455:Peptides