Advertisement

Journal of Molecular Medicine

, Volume 81, Issue 1, pp 43–50 | Cite as

HLA-A3 restricted mutant ras specific cytotoxic T-lymphocytes induced by vaccination with T-helper epitopes

  • Marianne Gjertsen
  • Ingvil Sæterdal
  • Stein Sæbøe-Larssen
  • Gustav Gaudernack
Original Article

Abstract.

Cytotoxic T-lymphocytes are one of the most important elements of the antitumor defense. Stimulation of cytotoxic T-lymphocytes outgrowth after immunization with mutant ras peptides is a desired goal since these cells may kill tumor cells in vivo. In this study we tested responding peripheral mononuclear cells from a patient with pancreatic adenocarcinoma who had received intradermal peptide vaccination with a mixture of 17-mer mutant ras peptides and granulocyte-macrophage colony-stimulating factor as an adjuvant. Responding peripheral T-cells were cloned by limiting dilution and several CD8+ cytotoxic T-lymphocytes, specific for the K-RAS 12-Cys mutation were obtained. By using a panel of nonamer peptides containing the 12-Cys mutation and covering position 4–21 in the ras molecule, the 9-mer peptide which was actually recognized by the cytotoxic T-lymphocytes could be identified. HLA-A*0302 could be identified as the antigen-presenting molecule, and the amino acid sequence of the T-cell epitope carries the previously identified HLA-A*0302 binding motif. The nonamer peptide was contained within the vaccine peptide originally used for intradermal immunization of the patient. The cytotoxic T-lymphocytes were capable of killing target cells expressing HLA-A*0302 that coexpressed the K-RAS 12-Cys mutation after transfection. These data demonstrate that the peptide used for vaccination (17-mer) is processed and presented in vivo, and that generation of cytotoxic T-lymphocytes by vaccination with T-helper epitopes may be important for further development of specific immunotherapy of cancer patients.

Cytotoxic T lymphocytes p21 ras Peptide vaccination Pancreatic cancer Granulocyte-macrophage colony-stimulating factor 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Marianne Gjertsen
    • 1
  • Ingvil Sæterdal
    • 1
  • Stein Sæbøe-Larssen
    • 1
  • Gustav Gaudernack
    • 1
  1. 1.Section for Immunotherapy, Department of Immunology, Norwegian Radium Hospital, University of Oslo, Montebello, 0310 Oslo, Norway

Personalised recommendations