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

D. Nagorsen, U. Keilholz, L. Rivoltini, A. Schmittel, A. Letsch, A. M. Asemissen, G. Berger, H. J. Buhr, E. Thiel, C. Scheibenbogen

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Abstract

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-γ 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-γ 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-γ+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.

Original languageEnglish
Pages (from-to)4850-4854
Number of pages5
JournalCancer Research
Volume60
Issue number17
Publication statusPublished - Sep 1 2000

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nagorsen, D., Keilholz, U., Rivoltini, L., Schmittel, A., Letsch, A., Asemissen, A. M., Berger, G., Buhr, H. J., Thiel, E., & Scheibenbogen, C. (2000). 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. Cancer Research, 60(17), 4850-4854.