Title
Engineering monocyte-derived dendritic cells to secrete interferon-<tex>$\alpha$</tex> enhances their ability to promote adaptive and innate anti-tumor immune effector functions Engineering monocyte-derived dendritic cells to secrete interferon-<tex>$\alpha$</tex> enhances their ability to promote adaptive and innate anti-tumor immune effector functions
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Heidelberg ,
Subject
Human medicine
Source (journal)
Cancer immunology and immunotherapy. - Heidelberg
Volume/pages
64(2015) :7 , p. 831-842
ISSN
0340-7004
ISI
000356875000004
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/541141/608ab9de43d.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/29b2b9/10491.pdf
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