A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells
Natural killer (NK) cells, members of the innate immune system, play an important role in the rejection of HLA class I negative tumor cells. Hence, a therapeutic vaccine, which can activate NK cells in addition to cells of the adaptive immune system might induce a more comprehensive cellular respons...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10227 |
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| author | Naomi C. Bosch Lena-Marie Martin Caroline J. Voskens Carola Berking Barbara Seliger Gerold Schuler Niels Schaft Jan Dörrie |
| author_facet | Naomi C. Bosch Lena-Marie Martin Caroline J. Voskens Carola Berking Barbara Seliger Gerold Schuler Niels Schaft Jan Dörrie |
| author_sort | Naomi C. Bosch |
| collection | DOAJ |
| description | Natural killer (NK) cells, members of the innate immune system, play an important role in the rejection of HLA class I negative tumor cells. Hence, a therapeutic vaccine, which can activate NK cells in addition to cells of the adaptive immune system might induce a more comprehensive cellular response, which could lead to increased tumor elimination. Dendritic cells (DCs) are capable of activating and expanding NK cells, especially when the NFκB pathway is activated in the DCs thereby leading to the secretion of the cytokine IL-12. Another prominent NK cell activator is IL-15, which can be bound by the IL-15 receptor alpha-chain (IL-15Rα) to be transpresented to the NK cells. However, monocyte-derived DCs do neither secrete IL-15, nor express the IL-15Rα. Hence, we designed a chimeric protein consisting of IL-15 and the IL-15Rα. Upon mRNA electroporation, the fusion protein was detectable on the surface of the DCs, and increased the potential of NFκB-activated, IL-12-producing DC to activate NK cells in an autologous cell culture system with ex vivo-generated cells from healthy donors. These data show that a chimeric IL-15/IL-15Rα molecule can be expressed by monocyte-derived DCs, is trafficked to the cell surface, and is functional regarding the activation of NK cells. These data represent an initial proof-of-concept for an additional possibility of further improving cellular DC-based immunotherapies of cancer. |
| first_indexed | 2024-03-10T07:00:33Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:33Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1b10a35c90e147a6ae282a039d1fac9b2023-11-22T16:06:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191022710.3390/ijms221910227A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer CellsNaomi C. Bosch0Lena-Marie Martin1Caroline J. Voskens2Carola Berking3Barbara Seliger4Gerold Schuler5Niels Schaft6Jan Dörrie7Institute of Medical Immunology, Martin-Luther University Halle-Wittenberg, 06112 Halle (Saale), GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Medical Immunology, Martin-Luther University Halle-Wittenberg, 06112 Halle (Saale), GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, GermanyNatural killer (NK) cells, members of the innate immune system, play an important role in the rejection of HLA class I negative tumor cells. Hence, a therapeutic vaccine, which can activate NK cells in addition to cells of the adaptive immune system might induce a more comprehensive cellular response, which could lead to increased tumor elimination. Dendritic cells (DCs) are capable of activating and expanding NK cells, especially when the NFκB pathway is activated in the DCs thereby leading to the secretion of the cytokine IL-12. Another prominent NK cell activator is IL-15, which can be bound by the IL-15 receptor alpha-chain (IL-15Rα) to be transpresented to the NK cells. However, monocyte-derived DCs do neither secrete IL-15, nor express the IL-15Rα. Hence, we designed a chimeric protein consisting of IL-15 and the IL-15Rα. Upon mRNA electroporation, the fusion protein was detectable on the surface of the DCs, and increased the potential of NFκB-activated, IL-12-producing DC to activate NK cells in an autologous cell culture system with ex vivo-generated cells from healthy donors. These data show that a chimeric IL-15/IL-15Rα molecule can be expressed by monocyte-derived DCs, is trafficked to the cell surface, and is functional regarding the activation of NK cells. These data represent an initial proof-of-concept for an additional possibility of further improving cellular DC-based immunotherapies of cancer.https://www.mdpi.com/1422-0067/22/19/10227adoptive cellular immunotherapyIL-15natural killer celldendritic cellNF-κB |
| spellingShingle | Naomi C. Bosch Lena-Marie Martin Caroline J. Voskens Carola Berking Barbara Seliger Gerold Schuler Niels Schaft Jan Dörrie A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells International Journal of Molecular Sciences adoptive cellular immunotherapy IL-15 natural killer cell dendritic cell NF-κB |
| title | A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells |
| title_full | A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells |
| title_fullStr | A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells |
| title_full_unstemmed | A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells |
| title_short | A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells |
| title_sort | chimeric il 15 il 15rα molecule expressed on nfκb activated dendritic cells supports their capability to activate natural killer cells |
| topic | adoptive cellular immunotherapy IL-15 natural killer cell dendritic cell NF-κB |
| url | https://www.mdpi.com/1422-0067/22/19/10227 |
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