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Clinical experiences with therapeutic DC vaccines targeting autologous cancer stem cells in glioblastoma

      Recent data suggest that the growth and recurrences of cancer after standard therapy is caused by a subpopulation of cells defined as cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal and has in spite of radical surgery followed by radiotherapy and chemotherapy, a median survival of less than one year. These clinical observations together with laboratory studies suggest that Glioblastoma is a CSCs disorder. Here we present our clinical experiences on patients treated with a dendritic cell (DC) based vaccine targeting CSCs in Glioblastoma. Brain tumor biopsies were dissociated into single cell suspensions, and autologous CSCs were expanded in vitro as tumourspheres. From these, CSC-mRNA were amplified and transfected by electroporation into monocyte-derived autologous DCs. The DCs were aliquoted to 12-18 vaccines containing 10e7 cells each, frozen and stored at liquid nitrogen until use. Following thawing and washing the DCs were injected intradermally at specified intervals after the patients had received the standard six weeks course of postoperative radio-chemotherapy. Altogether 22 patients have been included in the study. Here we report on the clinical effects of our first seven patients that could be weaned of corticosteroids and receive DC immunotherapy. Objective immune response induced by vaccination was confirmed in six patients. No patients developed adverse autoimmune events or other side effects. Compared to matched controls, vaccinated patients had 2.9 times longer progression free-survival (median 661 days vs. 226 days, p = 0.0018, Log-rank test). These preliminary findings suggest that vaccination against Glioblastoma stem cells is safe, well tolerated, and prolong recurrence free survival.
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