Rationale: Earlier we have demonstrated that dendritic cell-based immunotherapy induced protective antitumor immunity with prolonged survival in mice. However, the clinical relevance is still questioned. We designed a clinical trial using chemotherapy followed by antigen-pulsed dendritic cell vaccination in mesothelioma patients Objectives: The aim of this study was to assess the safety and immunological response induced by the administration of tumor lysate-pulsed dendritic cells in mesothelioma patients. Methods: Ten patients with malignant pleural mesothelioma received three vaccinations of clinical-grade autologous dendritic cells intradermally and intravenously at two-week intervals after chemotherapy. Each vaccine was composed of 50x10⁶ mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) as surrogate marker. Delayed-type hypersensitivity activity to tumor antigens and KLH was assessed, both in vivo and in vitro. Peripheral blood mononuclear cells during the treatment were analyzed for immunological responses. Main Results: Administration of dendritic cells pulsed with autologous tumor lysate in mesothelioma patients was safe with moderate fever as the only side effect. There were no grade 3 or 4 toxicities associated with the vaccines or any evidence of autoimmunity. Local accumulations of infiltrating T cells were found at the site of vaccination. The vaccinations induced distinct immunological responses to KLH, both in vitro and in vivo. Importantly, after three vaccinations, cytotoxic activity against autologous tumor cells was detected in a subgroup of patients. Conclusions: This study demonstrated that autologous tumor lysate-pulsed dendritic cell-based therapy is feasible, well-tolerated, and capable of inducing immunological response to tumor cells in mesothelioma patients. www.clinicaltrials.gov NCT00280982