RNA‐containing adenovirus/polyethylenimine transfer complexes effectively transduce dendritic cells and induce antigen‐specific T cell responses

Gust, Tatjana C; Diebold, Sandra S.; Cotten, Matthew; Zenke, Martin

doi:10.1002/jgm.492

Cited by 7 publications

(7 citation statements)

References 54 publications

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“…In our previous work cells were gene-modified and endowed with novel and wanted properties for use in medical therapy [7][8][9][10][11][12][13][14]. The application of such engineered cells is expected to become a routine in future medicine.…”

Section: Introductionmentioning

confidence: 99%

Uptake of magnetic nanoparticles into cells for cell tracking

Becker

Hodenius

Blendinger

et al. 2007

Journal of Magnetism and Magnetic Materials

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Section: Introductionmentioning

confidence: 99%

Uptake of magnetic nanoparticles into cells for cell tracking

Becker

Hodenius

Blendinger

et al. 2007

Journal of Magnetism and Magnetic Materials

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“…Plasmid DNA electroporation was found to be not applicable for tumour antigen loading of DCs because DCs electroporated with antigen plasmid DNA were unable to stimulate T cells in an antigen-specific manner. Inefficient DNA delivery into DCs and ineffective CD4 + and CD8 + T cell stimulation by DNA-transduced DCs have been also reported by the authors' group and others using different transfection systems [43,61]. Thus, electroporation of DCs with RNA is the most powerful method for high transfection efficiency and strong stimulation of T cell responses identified so far.…”

Section: Optimisation Of Rna Transductionmentioning

confidence: 56%

“…These structures increase RNA stability and prevent RNA degradation, as well as mediating the recruitment of the 40S and 60S ribosomal subunits and of eukaryotic translation initiation factors. The authors' group and others studied the effect of RNA-stabilising components, such as the cap structure and the polyA + tail, and found that capping and polyadenylation of RNA is critical for efficient antigen presentation and antigen-specific stimulation of T cells by RNA-transduced DCs [53,61,66]. DCs transduced with capped and polyadenylated RNA most likely produce higher levels of antigen than DCs transduced with uncapped and non-polyadenylated RNA.…”

Section: Optimisation Of Rna Transductionmentioning

confidence: 96%

“…Boczkowski et al [28] Splenic DC OVA RNA Lipofection CD8 + Ashley et al [29] BMDC Murine melanoma RNA Lipofection CD8 + Nair et al [30] MoDC CEA RNA Passive pulsing, electroporation CD4 + /CD8 + Heiser et al [40,41] MoDC PSA RNA Passive pulsing CD8 + Koido et al [46] BMDC MUC1 RNA Lipofection CD8 + Nair et al [35] BMDC MoDC TERT RNA Passive pulsing CD8 + Strobel et al [43] MoDC IMP RNA Lipofection, electroporation CD8 + Thornburg et al [47] MoDC HPV E6, E7 RNA Lipofection CD8 + Weissman et al [42] MoDC HIV gag RNA Lipofection CD4 + /CD8 + Schmitt et al [48] MoDC Bladder tumour RNA Passive pulsing CD8 + Eppler et al [49] MoDC CEA RNA Electroporation CD8 + Van Tendeloo et al [50] MoDC, CD34 DC, LC Melan-A RNA Electroporation, lipofection, passive pulsing CD8 + Kalady et al [51] MoDC Mart-1/Melan-A RNA Passive pulsing, lipofection, electroporation CD8 + Ponsaerts et al [52] MoDC IMP RNA Electroporation CD8 + Saebøe-Larssen et al [53] MoDC TERT RNA Electroporation CD8 + Su et al [36] MoDC TERT RNA Lipofection CD4 + /CD8 + Van Meirvenne et al [54] BMDC OVA RNA Electroporation CD4 + /CD8 + Grunebach et al [55] MoDC Renal cell carcinoma RNA Electroporation CD8 + Milazzo et al [56] MoDC Myeloma RNA Electroporation CD8 + Muller et al [57] MoDC Tumour RNA (breast and renal cancer) Electroporation CD4 + /CD8 + Nencioni et al [45] MoDC Colorectal tumour RNA Electroporation CD8 + Schmidt et al [58] BMDC Pancreatic tumour RNA Lipofection CD4 + /CD8 + Tuyaerts et al [59] MoDC MelanA, IMP RNA Electroporation CD8 + Zeis et al [38] BMDC MoDC Survivin RNA Lipofection CD8 + Bonehill et al [60] MoDC MAGE-3 RNA Electroporation CD4 + /CD8 + Gust et al [61] BMDC OVA RNA Ad/PEI CD4 + /CD8 + Kalady et al [62] MoDC CEA/Pancreatic tumour RNA Electroporation Muller et al [63] MoDC After the first Phase I study by Heiser and colleagues [44], Morse and co-workers …”

Section: Preclinical Study DC Type Type Of Antigen Rna Transfection Tmentioning

confidence: 99%

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RNA transfer and its use in dendritic cell-based immunotherapy

Gust

Zenke²

2005

Expert Opinion on Biological Therapy

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RNA is a key macromolecule for the mobilisation and interpretation of genetic information. Research has sought to exploit the inherent properties of RNA, such as the direct production of proteins in the cytoplasm without the need for nuclear translocation. This property makes the delivery of genes into postmitotic cells especially attractive. Recently, RNA transfer into postmitotic dendritic cells (DCs) has emerged as a potential new therapeutic agent in the area of immunotherapy. DCs are the most important regulators of the immune system. Thus, transfecting DCs with RNA allows the specific manipulation of immune responses and, thereby, the treatment of a variety of diseases, such as cancer. Preclinical studies have demonstrated that RNA-transduced DCs efficiently stimulate antigen-specific T cell responses in vitro and in animal tumour models. In addition, the clinical data from Phase I and II trials of tumour patients indicate that RNA-transduced DCs represent a promising approach for the development of future vaccination strategies. The use of RNA molecules as therapeutic agents is a relatively new approach in the treatment of diseases, such as cancer, but has received increasing attention during the past decade. Especially in the field of immunotherapy, the inherent properties of RNA molecules in combination with immunostimulating dendritic cells (DCs) are being investigated at present for their beneficial therapeutic effect. Immunotherapy is based on the stimulation of the patient's immune system to recognise and eliminate infected cells or tumour cells in an antigen-specific manner. Current approaches focus on the stimulation of CD8(+) cytotoxic T lymphocyte responses, as well as on the induction of CD4(+) T helper cell responses, in order to obtain optimal and sustained immune responses capable of eliminating altered cells. This review mainly focuses on the potential use of RNA-transduced DCs as a therapeutic strategy in the treatment of cancer, as current studies on the treatment of infectious diseases are just beginning.

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“…The design of polymeric carriers for such differential display of ODN ligands was based on several considerations. Although positively charged polymers such as poly(ethylene amine) have been widely used as nucleic acid carriers, in order to promote condensation and protection of the nucleic acid, the passage of the nucleic acids through cellular membranes into the cytosolic space is mediated at least in part through the interactions of the positively charged polyplex with the negatively charged cellular membrane[46–48]. Such nonspecific interaction of the conjugates with cellular membranes is undesirable in the current studies, as the goal is to probe the role of ODN display in the TLR9-mediated activation of immune cells without complications of interactions with the polymer scaffold.…”

Section: Resultsmentioning

confidence: 99%

DNA–polymer conjugates for immune stimulation through Toll-like receptor 9 mediated pathways

Levenson¹,

Kiick²

2014

Acta Biomaterialia

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Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotide motifs are agonists of Toll-like receptor 9 and are currently being investigated for use as vaccine adjuvants through promotion of type I immunity. Several classes of ODN have been developed which differ in their propensity to aggregate, which in turn, alter cytokine profiles and cellular subsets activated. Although aggregation state is correlated with the change in cytokine response, it is unknown if this results from a change in the number of ODN available for binding and/or the possible engagement of multiple TLR9 molecules. Here, we examined the role of ligand valency on the activation of TLR9 through the synthesis of ODN-poly(acrylic acid) (PAA) conjugates. The compositions and size of the conjugates were characterized by UV-Vis spectroscopy, 1H NMR, gel permeation chromatography, and dynamic light scattering. ELISA-based assays of cytokine secretion by murine-like macrophages indicate that these ODN-PAA polymer conjugates show enhanced immunostimulation at 100-fold lower concentrations than those required for ODN alone, for both TNF-α and IL-6 release, and are more potent than any other previously reported multivalent ODN constructs. Increasing valency was shown to significantly enhance cytokine expression, particularly for IL-6. Knockdown by siRNA demonstrates that these polymer conjugates are specific to TLR9. Our results define valency as a critical design parameter and polymer conjugation as an advantageous strategy for producing ODN immunomodulatory agents.

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RNA‐containing adenovirus/polyethylenimine transfer complexes effectively transduce dendritic cells and induce antigen‐specific T cell responses

Abstract: Ad/PEI/RNA transfection is an efficient means for generating RNA-transduced DCs and for stimulating antigen-specific T cell responses. Polyadenylation of RNA enhances CD8(+) T cell responses and is essential for CD4(+) T cell responses.

Cited by 7 publications

References 54 publications

Uptake of magnetic nanoparticles into cells for cell tracking

Uptake of magnetic nanoparticles into cells for cell tracking

RNA transfer and its use in dendritic cell-based immunotherapy

DNA–polymer conjugates for immune stimulation through Toll-like receptor 9 mediated pathways

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