Induction of tyrosinase-reactive T cells by treatment with dacarbazine, cisplatin, interferon-alpha +/- interleukin-2 in patients with metastatic melanoma

Int J Cancer. 1999 Jan 5;80(1):39-43. doi: 10.1002/(sici)1097-0215(19990105)80:1<39::aid-ijc8>;2-y.


We have shown the presence of tyrosinase-reactive T cells in the peripheral blood of melanoma patients, who had been in remission after treatment with IL-2-containing regimens. In this consecutive study, we analyzed the T-cell response to various peptides derived from tyrosinase in serial blood samples obtained from 7 stage-IV melanoma patients before, during and following treatment. All patients were treated within a randomized trial (EORTC 18951) with cisplatin (CDDP), dacarbazine (DTIC), interferon-alpha (IFN-alpha) +/- interleukin-2 (IL-2). Using an ELISPOT assay detecting peptide-specific IFN-gamma release, we measured the T-cell response to 4 different HLA class I-binding peptide epitopes derived from tyrosinase containing an HLA-A2.1-, HLA-A24- or HLA-B44-binding motif in peripheral-blood mononuclear cells (PBMC). In one patient, tyrosinase-reactive T cells were detected before therapy. In 4 out of 7 patients, tyrosinase-reactive T cells against both HLA-A2.1-binding peptides and the B44-binding peptide became detectable at frequencies of up to 30 in 5 x 10(5) lymphocytes following treatment. These patients received CDDP, DTIC and IFN-alpha, 2 of them without IL-2 and 2 with IL-2, resulting in one complete remission and 3 partial remissions. Two patients relapsed 8 and 9 months after treatment. At the time of relapse, no T cells reactive with tyrosinase were detectable. Our results show that high frequencies of tyrosinase-reactive T cells in the peripheral blood of melanoma patients can be induced by chemotherapy in combination with IFN-alpha, regardless of concomitant IL-2 administration.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Dacarbazine / administration & dosage
  • Epitopes / chemistry
  • Epitopes / immunology
  • HLA-A Antigens / immunology
  • HLA-B Antigens / immunology
  • HLA-B44 Antigen
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / therapeutic use*
  • Melanoma / enzymology
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Monophenol Monooxygenase / chemistry
  • Monophenol Monooxygenase / immunology*
  • Neoplasm Staging
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*


  • Epitopes
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-B44 Antigen
  • Interferon-alpha
  • Interleukin-2
  • Peptide Fragments
  • Dacarbazine
  • Interferon-gamma
  • Monophenol Monooxygenase
  • Cisplatin