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Title
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Engineering monocyte-derived dendritic cells to secrete interferon- enhances their ability to promote adaptive and innate anti-tumor immune effector functions
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Author
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Abstract
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| Dendritic cell (DC) vaccination has demonstrated potential in clinical trials as a new effective cancer treatment, but objective and durable clinical responses are confined to a minority of patients. Interferon (IFN)-α, a type-I IFN, can bolster anti-tumor immunity by restoring or increasing the function of DCs, T cells and natural killer (NK) cells. Moreover, type-I IFN signaling on DCs was found to be essential in mice for tumor rejection by the innate and adaptive immune system. Targeted delivery of IFN-α by DCs to immune cells could boost the generation of anti-tumor immunity, while avoiding the side effects frequently associated with systemic administration. Naturally circulating plasmacytoid DCs, major producers of type-I IFN, were already shown capable of inducing tumor antigen-specific T cell responses in cancer patients without severe toxicity, but their limited number complicates their use in cancer vaccination. In the present work, we hypothesized that engineering easily generated human monocyte-derived mature DCs to secrete IFN-α using mRNA electroporation enhances their ability to promote adaptive and innate anti-tumor immunity. Our results show that IFN-α mRNA electroporation of DCs significantly increases the stimulation of tumor antigen-specific cytotoxic T cell as well as anti-tumor NK cell effector functions in vitro through high levels of IFN-α secretion. Altogether, our findings mark IFN-α mRNA-electroporated DCs as potent inducers of both adaptive and innate anti-tumor immunity and pave the way for clinical trial evaluation in cancer patients. |
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Language
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English
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Source (journal)
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Cancer immunology and immunotherapy. - Heidelberg
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Publication
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Heidelberg
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2015
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ISSN
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0340-7004
[print]
1432-0851
[online]
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DOI
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10.1007/S00262-015-1688-2
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Volume/pages
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64
:7
(2015)
, p. 831-842
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ISI
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000356875000004
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Pubmed ID
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25863943
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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