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

✍ Scribed by Alexander Schmittel; Ulrich Keilholz; Regina Max; Eckhard Thiel; Carmen Scheibenbogen

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 92 KB
• Volume: 80
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990105)80:1<39::aid-ijc8>3.0.co;2-y

✦ Synopsis

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-␣ (IFN-␣) ؎ interleukin-2 (IL-2). Using an ELISPOT assay detecting peptidespecific IFN-␥ 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-B44binding 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 B44binding peptide became detectable at frequencies of up to 30 in 5 ؋ 10 5 lymphocytes following treatment. These patients received CDDP, DTIC and IFN-␣, 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-␣, regardless of concomitant IL-2 administration. Int.