Ras E, van der Burg S H, Zegveld S T, Brandt R M, Kuppen P J, Offringa R, Warnarr S O, van de Velde C J, Melief C J
Department of Immunohaematology and Blood Bank, University Hospital Leiden, The Netherlands.
Hum Immunol. 1997 Mar;53(1):81-9. doi: 10.1016/S0198-8859(97)00032-3.
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-A0201) 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-A0201 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.
与正常上皮细胞相比，上皮来源肿瘤细胞上上皮细胞粘附分子（Ep-CAM）和癌胚抗原（CEA）的表达模式改变，可能使T细胞优先识别并裂解这些肿瘤细胞。对410条Ep-CAM衍生序列（包括一组重叠的9个氨基酸长的肽段）和73条符合HLA-A0201基序的CEA衍生肽段，测试了它们与人白细胞抗原A2.1（HLA-A0201）的结合亲和力以及与该分子形成稳定肽-主要组织相容性复合体（MHC）相互作用的能力。随后，对具有高结合亲和力和低肽-MHC解离率的肽段在HLA-A*0201Kb转基因小鼠中测试其免疫原性。一条Ep-CAM衍生肽段和一条CEA衍生肽段能够在这些小鼠中可重复地诱导肽特异性细胞毒性T细胞（CTL）。这表明EpCAM和CEA是上皮癌CTL介导免疫治疗的潜在靶抗原。
