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March 04, 2010

Progress to a Vaccine Against Malignant Mesothelioma

Researchers have demonstrated the safety of a potential vaccine against mesothelioma, a rare cancer associated primarily with asbestos exposure. (31 page pdf) The vaccine, which infuses uses a patient's own dendritic cells (DC) with antigen from the patient's tumor, was able to induce a T-cell response against mesothelioma tumors.

The U.S. and other developed countries have prohibited the use of asbestos for decades, but the time between asbestos exposure and diagnosis of mesothelioma can up to 50 years. The incidence of mesothelioma, therefore, is still on the rise and expected to continue to increase until 2020. Once diagnosed, mesothelioma has a median survival time of 12 months. The standard chemotherapeutic treatment only improves survival time by about three months.

Serum samples from all patients showed a significant increase of pre- versus post-vaccine antibodies to KLH. In the four patients whose tumor material was sufficient for testing, there was clear induction of cytotoxicity against their own tumors after vaccination. Three patients showed signs of tumor regression, though this could not be conclusively or directly attributed to the vaccine.

About 2,000 new cases of mesothelioma are diagnosed in the United States each year. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.





American Thoracic Society's American Journal of Respiratory and Critical Care Medicine - Consolidative Dendritic Cell-Based Immunotherapy Elicits Cytotoxicity Against Malignant Mesothelioma

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 50x10^6 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.


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