New generation of cancer vaccines based on IL-12 producing dendritic cells. Phase II clinical trial in patients with glioblastoma multiforme
| Authors | |
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| Year of publication | 2010 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Dendritic cells (DCs) capable of high interleukin-12 production are able to polarize the immune response towards type 1 helper T-cells and cytotoxic T-cells. Thus they maximize anti-cancer immune reaction. We validated the process of clinical-grade DC preparation under the Good Manufacturing Practice (GMP) conditions. Leukocyte apheresis product was obtained from 3 individuals and a fraction rich in monocytes was harvested by elutriation. Monocytes were cultured in complete medium supplemented with interleukin-4 and granulocyte macrophage colony-stimulating factor for 6 days. At this point, immature DCs were loaded with tumour antigens obtained from tumour lysate prepared by repeated freeze/thaw cycles of the tumour cells. DCs were matured by lipopolysaccharide and interferon-gamma, harvested and frozen in aliquots. The whole process of vaccine preparation was performed at certified GMP-facility of Babak Research Institute at Masaryk University. During the validation we were able to prepare DCs with high expression of CD80, CD83, CD86 and HLA-DR, low expression of CD14 and high production of interleukin-12. DCs were able to activate effectively proliferation of allogeneic T lymphocytes in an allogeneic mixed leukocyte reaction (see Table). Since November 2009, a phase II clinical trial using new generation of IL-12 producing DC-based vaccination in patients with primary glioblastoma is ongoing. Until May 2010, seven patients were included. First clinical experience with DC vaccination will be presented at the conference. Supported in part by MSMT NPVII 2B06058, MSMT NPVII 2B08066 and IGA NS9875-4. |
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