Cancer Immunology, Immunotherapy

, Volume 54, Issue 3, pp 219–228

Spontaneous T-cell responses against peptides derived from the Taxol resistance–associated gene-3 (TRAG-3) protein in cancer patients

  • Anders Meier
  • Sine Reker
  • Inge Marie Svane
  • Lars Holten-Andersen
  • Jürgen C. Becker
  • Ib Søndergaard
  • Mads Hald Andersen
  • Per thor Straten
Original Article

DOI: 10.1007/s00262-004-0578-9

Cite this article as:
Meier, A., Reker, S., Svane, I.M. et al. Cancer Immunol Immunother (2005) 54: 219. doi:10.1007/s00262-004-0578-9

Abstract

Expression of the cancer-testis antigen Taxol resistance–associated gene-3 (TRAG-3) protein is associated with acquired paclitaxel (Taxol) resistance, and is expressed in various cancer types; e.g., breast cancer, leukemia, and melanoma. Thus, TRAG-3 represents an attractive target for immunotherapy of cancer. To identify HLA-A*02.01–restricted epitopes from TRAG-3, we screened cancer patients for spontaneous cytotoxic T-cell responses against TRAG-3–derived peptides. The TRAG-3 protein sequence was screened for 9mer and 10mer peptides possessing HLA-A*02.01–binding motifs. Of 12 potential binders, 9 peptides were indeed capable of binding to the HLA-A*02.01 molecule, with binding affinities ranging from strong to weak binders. Subsequently, lymphocytes from cancer patients (9 breast cancer patients, 12 melanoma patients, and 13 patients with hematopoietic malignancies) were analyzed for spontaneous reactivity against the panel of peptides by ELISpot assay. Spontaneous immune responses were detected against 8 epitope candidates in 7 of 9 breast cancer patients, 7 of 12 melanoma patients, and 5 of 13 patients with hematopoietic malignancies. In several cases, TRAG-3–specific CTL responses were scattered over several epitopes. Hence, no immunodominance of any single peptide was observed. Furthermore, single-peptide responses were detected in 2 of 12 healthy HLA-A2+ donors, but no responses were detectable in 9 HLA-A2 healthy donors or 4 HLA-A2 melanoma patients. The identified HLA-A*02.01–restricted TRAG-3–derived epitopes are targets for spontaneous immune responses in breast cancer, hematopoietic cancer, and melanoma patients. Hence, these epitopes represent potential target structures for future therapeutic vaccinations against cancer, possibly appropriate for strategies that combine vaccination and chemotherapy; i.e., paclitaxel treatment.

Keywords

Cancer-testis antigenChemotherapyPeptideTumor-associated antigenTumor-specfic T cell

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Anders Meier
    • 1
  • Sine Reker
    • 1
  • Inge Marie Svane
    • 2
  • Lars Holten-Andersen
    • 1
  • Jürgen C. Becker
    • 3
  • Ib Søndergaard
    • 4
  • Mads Hald Andersen
    • 1
  • Per thor Straten
    • 1
  1. 1.Tumor Immunology Group, Danish Cancer SocietyInstitute for Cancer BiologyCopenhagenDenmark
  2. 2.Department of OncologyHerlev University HospitalHerlevDenmark
  3. 3.Department of DermatologyUniversity of WürzburgWürzburgGermany
  4. 4.BiocentrumTechnical University of DenmarkCopenhagenDenmark