Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells
G Schreibelt, D Benitez-Ribas… - Blood, The Journal …, 2010 - ashpublications.org
G Schreibelt, D Benitez-Ribas, D Schuurhuis, AJA Lambeck, M van Hout-Kuijer, N Schaft…
Blood, The Journal of the American Society of Hematology, 2010•ashpublications.orgCurrently 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 …
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 …
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.
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