Natural T-cell response against MHC class I epitopes of epithelial cell adhesion molecule, her-2/neu, and carcinoembryonic antigen in patients with colorectal cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 60; no. 17; pp. 4850 - 4854
• Main Authors: NAGORSEN, Dirk, KEILHOLZ, Ulrich, RIVOLTINI, Licia, SCHMITTEL, Alexander, LETSCH, Anne, ASEMISSEN, Anne Marie, BERGER, Gerd, BUHR, Heinz-Johannes, THIEL, Eckhard, SCHEIBENBOGEN, Carmen
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2000
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Carcinoembryonic Antigen - immunology; Cell Adhesion Molecules - immunology; Colorectal Neoplasms - blood; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Enzyme-Linked Immunosorbent Assay - methods; Epithelial Cell Adhesion Molecule; Epitopes, T-Lymphocyte - immunology; Female; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; HLA-A2 Antigen - immunology; Humans; Immunotherapy; Lymphocyte Activation - immunology; Male; Medical sciences; Neoplasm Staging; neu gene; Peptide Fragments - immunology; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Receptor, ErbB-2 - immunology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T-Lymphocytes - immunology; Tumors; Antineoplastic agent; Rectal disease; Carcinoma; Antigenic determinant; Major histocompatibility system; Cytotoxicity; Carcinoembryonic antigen; Target; Mononuclear cell; Ex vivo; Immunotherapy; T-Lymphocyte; Intestinal disease; Advanced stage; Colon; Class I histocompatibility antigen; Human; Immunostimulation; Immune response; Tumor associated antigen; Cell adhesion molecule; Malignant tumor; Epithelium; Colonic disease; Blood cell; Immunogenicity; C-Onc gene; Rectum; Digestive diseases
• ISSN: 0008-5472

The antigens epithelial cell adhesion molecule (Ep-CAM), her-2/neu, and carcinoembryonic antigen (CEA) are potential T-cell targets in antigen-specific vaccination-based cancer therapy. We performed this study to evaluate whether a natural specific T-cell response against these tumor-associated antigens (TAAs) already exists in patients with colorectal carcinoma (CRC). We used the IFN-gamma ELISPOT assay to detect circulating TAA-reactive T cells directly ex vivo in unstimulated peripheral blood mononuclear cells. We analyzed the T-cell response in peripheral blood mononuclear cells of 22 HLA-A2-positive patients with CRC and 8 HLA-A2-positive healthy subjects against 3 HLA A2-restricted peptide epitopes of the TAAs Ep-CAM (GLKAGVIAV), her-2/neu (IISAVVGIL), and CEA (YLSGANLNL). Seven of 22 patients but none of the 8 healthy subjects had T cells specifically secreting IFN-gamma in response to one to three of these antigens (n = 4, Ep-CAM; n = 5, her-2/neu; n = 6, CEA). In three of the seven responding patients, TAA-reactive T cells were further characterized by flow cytometry. In all three patients, the majority of these T cells have a CD3+CD8+IFN-gamma+CD69+CD45RA+ phenotype, resembling activated effector-type T cells. T-cell responses occurred only in patients with metastatic disease (Dukes' stages C and D). The results of this study indicate that natural T-cell responses against TAAs occur in approximately one-half of CRC patients with involvement of lymph nodes or distant metastases, but not in CRC patients with disease confined to the intestinum.