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Antigen-specific vaccination is a very promising new option for cancer patients. As reviewed by Jäger et al., results from early clinical vaccination trials are of interest, since induction of T-cell responses and even tumor regressions in a few patients were observed. Objective tumor remissions, however, were rarely observed in most studies performed so far (review in [1]) and were usually restricted to melanoma patients with limited disease. In the MAGE-3 peptide study cited by Jäger et al. with a 30% response rate, the 7 patients showing an objective tumor remission all had metastatic disease limited to soft tissue or lymph nodes and the response evaluation did not include the 14 patients with early progressive disease during vaccination [2]. Jäger et al. so far have published in 1996 only the results from 3 patients with objective tumor regression by peptide vaccination with GM-CSF [3], but since then not the results on further patients vaccinated with this protocol. In a recent two-center phase II trial, in which we had vaccinated 16 patients with metastatic melanoma with tyrosinase peptides and GM-CSF using similar dosages as Jäger et al., no objective tumor remissions were observed and T-cell responses were recorded in only 2 of 16 patients with a mixed response and a stable disease [4]. Future perspectives need to focus on more potent vaccination strategies. This can be either achieved using more potent molecular or cellular adjuvants or by vaccinating patients in an adjuvant situation or with minimal residual disease, as suggested by recent studies [5]. Systematic comparative development of vaccination strategies is urgently warranted, since so far its role in adjuvant and therapeutic situations remains undefined. This is best achieved in form of controlled clinical phase I–III trials as currently performed within the EORTC (European Organization for Research and Treatment), and the ADO (Arbeitsgemeinschaft Dermato-Onkologie). Also crucial for the development of antigen-specific vaccination are sensitive and standardized T-cell assays to monitor the induction of specific T-cell responses. Within the EORTC melanoma group we have performed several expert workshops on T-cell assay methodology and have evaluated different assays in a multicenter laboratory study showing the high sensitivity and reproducibility of the ELISPOT assay (introduced into the field by Thomas Woelfel) in contrast to chromium release CTL assays [6]. As a basis for a randomized adjuvant phase III trial, we have subsequently performed a series of phase I trials to evaluate the immunogenicity of different adjuvants in peptide-based vaccination. In two consecutive phase I trials we could not detect a difference in frequency, strength or duration of peptide-induced T-cell responses if peptides were applied alone or in combination with GM-CSF, using a similar schedule as reported by Jäger et al. [3], but we could show a strong adjuvant effect if immunogenic ‘T helper proteins’ were added as adjuvants [7]. Randomized phase III peptide vaccination trials will be activated shortly by the EORTC for patients with resected stage III and IV melanoma as well as for patients with highrisk ocular melanoma. In the USA, the ECOG (Eastern Cooperative Oncology Group) is following the same path and has recently activated a similar study evaluating the effect of peptide vaccination and the role of GM-CSF in a randomized phase III trial in stage IV patients after resection of metastases. In patients with metastatic melanoma the therapeutic efficacy of peptide vaccination with dendritic cells is currently being evaluated in a randomized trial against standard DTIC chemotherapy within the ADO. Before results from these ongoing studies are available, patients should be treated whenever possible within controlled multicenter trials to obtain reliable data on the role of antigenspecific immunotherapy in adjuvant and therapeutic cancer treatment. U. Keilholz, C. Scheibenbogen, E. Thiel, Berlin D. Schadendorf, Mannheim