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

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Publication year
2010Source
Blood, 116, 4, (2010), pp. 564-74ISSN
Publication type
Article / Letter to editor

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Organization
Tumorimmunology
Medical Oncology
Paediatrics - OUD tm 2017
Journal title
Blood
Volume
vol. 116
Issue
iss. 4
Page start
p. 564
Page end
p. 74
Subject
NCMLS 2: Immune Regulation; ONCOL 3: Translational researchAbstract
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 E(2) (PGE(2); vaccine PGE(2) DCs). Vaccine PGE(2) DCs are potent inducers of T-cell proliferation and induce Th1 polarization. In addition, vaccine PGE(2) DCs are potent inducers of tumor antigen-specific CD8(+) effector T cells. Finally, vaccine PGE(2)-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.
This item appears in the following Collection(s)
- Academic publications [227437]
- Electronic publications [107154]
- Faculty of Medical Sciences [86157]
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