Functional detection of epithelial cell adhesion molecule specific cytotoxic T lymphocytes in patients with lung cancer, colorectal cancer and in healthy donors.
Epithelial cell adhesion molecule (Ep-CAM) derived antigenic peptides have been identified that can be recognized by cytotoxic T lymphocytes (CTL) in a major histocompatibility complex (MHC) class I restricted fashion. Thus, altered expression of Ep-CAM in a variety of human tumors might render a potential target for T cell mediated therapy. We have examined, whether the novel HLA-A*0201 restricted peptide ILYENNVIT (184-192) corresponding to Ep-CAM and one heteroclitic modified variant peptide previously demonstrated to be immunogenic in the human system can elicit antigen specific CTL responses in HLA-A2 positive patients with history of Ep-CAM expressing cancer of lung and colon. Specific CTL recognition of T2 target cells pulsed with the native peptide as well as of the lung cancer cell line A549 indicates that an appropriate T cell repertoire can be expanded from peripheral blood from patients in clinical remission and with advanced cancer. Despite an overall low frequency, peptide specific precursor CTLs could be readily expanded from peripheral blood from 6/8 patients that were diagnosed previously with Ep-CAM expressing lung cancer and 4/8 control individuals (2/5 healthy donors and 2/3 colon cancer patients). CTLs from three of five lung cancer patients tested also lyzed the HLA-A2(+) and Ep-CAM expressing lung cancer cell line A549. We did not detect an increased frequency of pCTLs after peripheral blood monocytes (PBMCs) were stimulated with the heteroclitic compound peptide. The results of our study indicate that Ep-CAM specific precursor CTL can be expanded in vitro and a specific T cell response against this epitope can be elicited in patients at various stages of lung cancer.
Trojan
Andreas
A
Division of Oncology, Department of Internal Medicine, University Hospital Zürich, Rämistrasse 100, 8091, Switzerland. andreas.trojan@dim.usz.ch
Tun-Kyi
Adrian
A
Odermatt
Bernhard
B
Nestle
Frank O
FO
Stahel
Rolf A
RA
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D018288:Carcinoma, Small Cell / Q000276:immunology*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology*; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments