Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells

Breckpot, Karine; Heirman, Carlo; Neyns, Bart; Thielemans, Kris

doi:10.1002/jgm.615

Cited by 61 publications

(35 citation statements)

References 167 publications

(134 reference statements)

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“…Our study not only confirms these observations, but provides substantial additional information. First, adenovirus infection renders the DCs more mature and more immunogenic, whereas lentiviral transduction has no such effect [40]. Feili-Hariri et al reported an enhanced CD40, CD80 and CD86 expression, while these markers, as well as MHC class II, were not or minimally changed in our case.…”

Section: Discussionmentioning

confidence: 50%

Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice

Creusot

Yaghoubi²,

Kodama

et al. 2008

Clinical Immunology

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A deficit in IL-4 production has been previously reported in both diabetic human patients and nonobese diabetic (NOD) mice. In addition, re-introducing IL-4 into NOD mice systemically, or as a transgene, led to a beneficial outcome in most studies. Here, we show that prediabetic, 12-wk old female NOD mice have a deficit in IL-4 expression in the pancreatic lymph nodes (PLN) compared to age-matched diabetes-resistant NOD.B10 mice. By bioluminescence imaging, we demonstrated that the PLN was preferentially targeted by bone marrow-derived dendritic cells (DCs) following intravenous (IV) administration. Following IV injection of DCs transduced to express IL-4 (DC/ IL-4) into 12-wk old NOD mice, it was possible to significantly delay or prevent the onset of hyperglycemia. We then focused on the PLN to monitor, by microarray analysis, changes in gene expression induced by DC/IL-4 and observed a rapid normalization of the expression of many genes, that were otherwise under-expressed compared to NOD.B10 PLN. The protective effect of DC/IL-4 required both MHC and IL-4 expression by the DCs. Thus, adoptive cellular therapy, using DCs modified to express IL-4, offers an effective, tissue-targeted cellular therapy to prevent diabetes in NOD mice at an advanced stage of pre-diabetes, and may offer a safe approach to consider for treatment of high risk human pre-diabetic patients.

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Section: Discussionmentioning

confidence: 50%

Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice

Creusot

Yaghoubi²,

Kodama

et al. 2008

Clinical Immunology

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“…RNA encoding the immunoreceptors was transferred to T cells by electroporation, which is a vector-independent transfer system. RNA electroporation initially was used to modify dendritic cells to express tumor antigens 30,31 or to functionally manipulate these cells. 32,33 Subsequently, RNA electroporation was used to transfer full-length TCR to T cells to redirect them with a new specificity.…”

Section: Discussionmentioning

confidence: 99%

Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer

et al. 2009

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“…1-3). Several strategies have been developed to deliver TAAs to DCs, including the use of mRNA (4)(5)(6). Autologous DCs loaded ex vivo with TAA mRNA have been extensively tested in preclinical studies, showing their ability to induce functional T H 1 cells and CTLs (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Evaluation of TriMix and Antigen mRNA-Based Antitumor Therapy

Goyvaerts²,

et al. 2012

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The use of tumor-associated antigen (TAA) mRNA for therapeutic purposes is under active investigation. To be effective, mRNA vaccines need to deliver activation stimuli in addition to TAAs to dendritic cells (DC). In this study, we evaluated whether intranodal delivery of TAA mRNA together with TriMix, a mix of mRNA encoding CD40 ligand, constitutive active Toll-like receptor 4 and CD70, results in the in situ modification and maturation of DCs, hence, priming of TAA-specific T cells. We showed selective uptake and translation of mRNA in vivo by lymph node resident CD11c þ cells. This process was hampered by codelivery of classical maturation stimuli but not by TriMix mRNA. Importantly, TriMix mRNA induced a T-cell-attracting and stimulatory environment, including recruitment of antigen-specific CD4 þ and CD8 þ T cells and CTLs against various TAAs. In several mouse tumor models, mRNA vaccination was as efficient in CTL induction and therapy response as vaccination with mRNAelectroporated DCs. Together, our findings suggest that intranodal administration of TAA mRNA together with mRNA encoding immunomodulating molecules is a promising vaccination strategy. Cancer Res; 72(7); 1661-71. Ó2012 AACR.

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Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells

Cited by 61 publications

References 167 publications

Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice

Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice

Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer

Preclinical Evaluation of TriMix and Antigen mRNA-Based Antitumor Therapy

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