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Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells

2010; Elsevier BV; Volume: 116; Issue: 4 Linguagem: Inglês

10.1182/blood-2009-11-251884

1528-0020

Gerty Schreibelt, Daniel Benítez‐Ribas, Danita H. Schuurhuis, Annechien J.A. Lambeck, Maaike van Hout-Kuijer, Niels Schaft, Cornelis J.A. Punt, Carl G. Figdor, Gosse J. Adema, I. Jolanda M. de Vries,

Immune cells in cancer

Abstract Currently dendritic cell (DC)–based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limited availability of clinical-grade TLR ligands significantly hampers the translation of these findings into DC-based vaccines. Therefore, we explored 15 commonly used preventive vaccines as a possible source of TLR ligands. We have identified a cocktail of the vaccines BCG-SSI, Influvac, and Typhim that contains TLR ligands and is capable of optimally maturing DCs. These DCs (vaccine DCs) showed high expression of CD80, CD86, and CD83 and secreted interleukin-12. Although vaccine DCs exhibited an impaired migratory capacity, this could be restored by addition of prostaglandin E2 (PGE2; vaccine PGE2 DCs). Vaccine PGE2 DCs are potent inducers of T-cell proliferation and induce Th1 polarization. In addition, vaccine PGE2 DCs are potent inducers of tumor antigen-specific CD8+ effector T cells. Finally, vaccine PGE2–induced DC maturation is compatible with different antigen-loading strategies, including RNA electroporation. These data thus identify a new clinical application for a mixture of commonly used preventive vaccines in the generation of Th1-inducing clinical-grade mature DCs.