Dendritic Cell-based Vaccine for Complementary Therapy of High Grade Glioma Patients using the CliniMACS Platform for Large-scale Clinical Production
L. Adamson1*, G. Stragliotto2, G. Giraud3, B. Näsman-Glaser1, R. Kiessling1K. Heimersson1, S. v Gool4,S. Holm3 and J-I Henter3
1Dept. of Oncology & Pathology, Cancer Centre Karolinska; 2Dept. of Neurosciences; 3Dept. of Woman and Child Health, Karolinska University Hospital, 171 76 Stockholm, Sweden; 4Laboratory of Pediatric Immunology, Dep. of Microbiology & Immunology, KU Leuven, Belgium *Corresponding author
The aim of the study is to improve treatment of children and young adults with high-grade glioma (HGG) with immune therapy based on vaccination with autologous dendritic cells (DC) loaded with tumour-derived lysate. As Clinical studies require protocols where a sufficient number of well characterized highly immunogenic dendritic cells are produced according to Good Manufacturing Practice (GMP) guidelines, we validated a large-scale production GMP platform of HGG-DC vaccines from a single leukapheresis product. We applied the CD14+ immunomagnetic selection using the CliniMACS platform for large-scale monocyte enrichment from a single leukapheresis product (n=10 patients) as starting material. Collected fractions were analysed for cell specificities with a panel of surface markers by flow cytometry. The monocyte fractions were differentiated into immature DC in culture bags using GM-CSF and IL-4 and loaded with tumour derived lysate to mature DC using TNF alfa. DC-generation was determined using phenotypic markers and collected blood samples analyzed with functional assays (FASCIA) and cytokine arrays. Our results show that the HGG-DC production platform is very robust and reproducible resulting in high monocyte purity, high recovery and a mature phenotype. Delivered vaccines show a high and reproducible quality. According to the previous results in the HGG-2003 and HGG-2006 trials in Leuven, and in collaboration with the Belgian group, this study aims at improving the survival for Swedish children and adults with High Grade Glioma.
This work was supported by The Swedish Childhood Cancer Foundation.