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

Arianna Bonomi, Daniela Lisini, Stefania Elena Navone, Simona Frigerio, Marta Dossena, Emilio Ciusani, Paolo Rampini, Giovanni Marfia, Valentina Coccè, Loredana Cavicchini, Francesca Sisto, Eugenio Parati, Renato Mantegazza, Marco Rimoldi, Manuela Rizzetto, Giulio Alessandri, Augusto Pessina

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)310-319
Number of pages10
JournalCytotherapy
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Keywords

  • CD14+ cells
  • Drug uptake
  • Glioblastoma
  • Taxol

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Oncology
  • Genetics(clinical)
  • Transplantation
  • Cancer Research
  • Cell Biology

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