Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells
For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs) is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs). However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and indu...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/952184 |
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| author | Stefanie Hoyer Kerstin F. Gerer Isabell A. Pfeiffer Sabrina Prommersberger Sandra Höfflin Tanushree Jaitly Luca Beltrame Duccio Cavalieri Gerold Schuler Julio Vera Niels Schaft Jan Dörrie |
| author_facet | Stefanie Hoyer Kerstin F. Gerer Isabell A. Pfeiffer Sabrina Prommersberger Sandra Höfflin Tanushree Jaitly Luca Beltrame Duccio Cavalieri Gerold Schuler Julio Vera Niels Schaft Jan Dörrie |
| author_sort | Stefanie Hoyer |
| collection | DOAJ |
| description | For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs) is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs). However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs’ immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1), and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFα of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-κB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs. |
| format | Article |
| id | doaj-art-1337b1edfd5747f8a02a17314f113630 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1337b1edfd5747f8a02a17314f1136302025-02-03T01:20:14ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/952184952184Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic CellsStefanie Hoyer0Kerstin F. Gerer1Isabell A. Pfeiffer2Sabrina Prommersberger3Sandra Höfflin4Tanushree Jaitly5Luca Beltrame6Duccio Cavalieri7Gerold Schuler8Julio Vera9Niels Schaft10Jan Dörrie11Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, ItalyDepartment of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, ItalyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Erlangen, GermanyFor therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs) is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs). However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs’ immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1), and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFα of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-κB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs.http://dx.doi.org/10.1155/2015/952184 |
| spellingShingle | Stefanie Hoyer Kerstin F. Gerer Isabell A. Pfeiffer Sabrina Prommersberger Sandra Höfflin Tanushree Jaitly Luca Beltrame Duccio Cavalieri Gerold Schuler Julio Vera Niels Schaft Jan Dörrie Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells Journal of Immunology Research |
| title | Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells |
| title_full | Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells |
| title_fullStr | Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells |
| title_full_unstemmed | Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells |
| title_short | Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells |
| title_sort | electroporated antigen encoding mrna is not a danger signal to human mature monocyte derived dendritic cells |
| url | http://dx.doi.org/10.1155/2015/952184 |
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