Human CD14+ cells loaded with Paclitaxel inhibit in vitro cell proliferation of glioblastoma

• Published in: Cytotherapy (Oxford, England) England), 2015-03, Vol.17 (3), p.310-319
• Main Authors: Bonomi, Arianna, Lisini, Daniela, Navone, Stefania Elena, Frigerio, Simona, Dossena, Marta, Ciusani, Emilio, Rampini, Paolo, Marfia, Giovanni, Coccè, Valentina, Cavicchini, Loredana, Sisto, Francesca, Parati, Eugenio, Mantegazza, Renato, Rimoldi, Marco, Rizzetto, Manuela, Alessandri, Giulio, Pessina, Augusto
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Antineoplastic Agents - administration & dosage; Cancer Vaccines - metabolism; CD14+ cells; Cell Differentiation - drug effects; Cell Line; Cell Proliferation; Cell- and Tissue-Based Therapy; Culture Media, Conditioned - pharmacology; Dendritic Cells - immunology; Drug Delivery Systems; drug uptake; glioblastoma; Glioblastoma - immunology; Glioblastoma - pathology; Glioblastoma - therapy; Humans; Lipopolysaccharide Receptors - analysis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells; Other; Paclitaxel - administration & dosage; Taxol
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2014.09.009

Abstract Background aims In attempting to develop new strategies to circumvent the immunosuppression associated with glioblastoma (GB), novel approaches have been designed using dendritic cell (DC)-based vaccination, which is considered a promising strategy to attack high-grade glioma. In previous studies, we demonstrated that human mesenchymal stromal cells without genetic manipulation but primed with Paclitaxel (PTX) acquire a potent anti-tumor activity, providing an interesting new biological approach for drug delivery. On the basis of these results, we here investigated whether both CD14+ and their derived DCs may behave like mesenchymal stromal cells acquiring anti-tumor activity on priming with PTX. Methods Human CD14+ cells were isolated from peripheral blood. Fluorescence-activated cell sorter analysis was performed to determine the purity of CD14+ and their differentiation into mature DCs. Cells were primed by incubation with 1 μg/mL of PTX for 24 h, and the PTX released by cells was assessed by mass spectrometry analysis. Anti-tumor activity was checked by testing the conditioned medium (CM) on the proliferation of U87 MG, a GB cell line. Results Both CD14+ and DCs were able to incorporate PTX and release the drug in the CM in a time-dependent manner (maximal release over 24 h). The addition of CM from CD14+ and DCs loaded with PTX strongly inhibits proliferation of U87 MG cells. Conclusions Our results are the first demonstration that peripheral blood–derived CD14+ and DCs, in addition to their application for immunotherapy for GB, could also be used to delivery anti-cancer drugs, such as PTX, to kill GB cells.