Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use
Personalized dendritic cell- (DC-) based vaccination has proven to be safe and effective as second-line therapy against various cancer types. In terms of overall survival, there is still room for improvement of DC-based therapies, including the development of more immunostimulatory DC vaccines. In t...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/1975902 |
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| author | J. M. J. Van den Bergh E. L. J. M. Smits M. Versteven H. De Reu Z. N. Berneman V. F. I. Van Tendeloo E. Lion |
| author_facet | J. M. J. Van den Bergh E. L. J. M. Smits M. Versteven H. De Reu Z. N. Berneman V. F. I. Van Tendeloo E. Lion |
| author_sort | J. M. J. Van den Bergh |
| collection | DOAJ |
| description | Personalized dendritic cell- (DC-) based vaccination has proven to be safe and effective as second-line therapy against various cancer types. In terms of overall survival, there is still room for improvement of DC-based therapies, including the development of more immunostimulatory DC vaccines. In this context, we redesigned our currently clinically used DC vaccine generation protocol to enable transpresentation of interleukin- (IL-) 15 to IL-15Rβγ-expressing cells aiming at boosting the antitumor immune response. In this study, we demonstrate that upon electroporation with both IL-15 and IL-15Rα-encoding messenger RNA, mature DC become highly positive for surface IL-15, without influencing the expression of prototypic mature DC markers and with preservation of their cytokine-producing capacity and their migratory profile. Functionally, we show that IL-15-transpresenting DC are equal if not better inducers of T-cell proliferation and are superior in tumor antigen-specific T-cell activation compared with DC without IL-15 conditioning. In view of the clinical use of DC vaccines, we evidence with a time- and cost-effective manner that clinical grade DC can be safely engineered to transpresent IL-15, hereby gaining the ability to transfer the immune-stimulating IL-15 signal towards antitumor immune effector cells. |
| format | Article |
| id | doaj-art-d6fd4348027445b69940c6e9b245677b |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-d6fd4348027445b69940c6e9b245677b2025-02-03T01:30:04ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/19759021975902Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical UseJ. M. J. Van den Bergh0E. L. J. M. Smits1M. Versteven2H. De Reu3Z. N. Berneman4V. F. I. Van Tendeloo5E. Lion6Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, BelgiumPersonalized dendritic cell- (DC-) based vaccination has proven to be safe and effective as second-line therapy against various cancer types. In terms of overall survival, there is still room for improvement of DC-based therapies, including the development of more immunostimulatory DC vaccines. In this context, we redesigned our currently clinically used DC vaccine generation protocol to enable transpresentation of interleukin- (IL-) 15 to IL-15Rβγ-expressing cells aiming at boosting the antitumor immune response. In this study, we demonstrate that upon electroporation with both IL-15 and IL-15Rα-encoding messenger RNA, mature DC become highly positive for surface IL-15, without influencing the expression of prototypic mature DC markers and with preservation of their cytokine-producing capacity and their migratory profile. Functionally, we show that IL-15-transpresenting DC are equal if not better inducers of T-cell proliferation and are superior in tumor antigen-specific T-cell activation compared with DC without IL-15 conditioning. In view of the clinical use of DC vaccines, we evidence with a time- and cost-effective manner that clinical grade DC can be safely engineered to transpresent IL-15, hereby gaining the ability to transfer the immune-stimulating IL-15 signal towards antitumor immune effector cells.http://dx.doi.org/10.1155/2017/1975902 |
| spellingShingle | J. M. J. Van den Bergh E. L. J. M. Smits M. Versteven H. De Reu Z. N. Berneman V. F. I. Van Tendeloo E. Lion Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use Journal of Immunology Research |
| title | Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use |
| title_full | Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use |
| title_fullStr | Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use |
| title_full_unstemmed | Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use |
| title_short | Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use |
| title_sort | characterization of interleukin 15 transpresenting dendritic cells for clinical use |
| url | http://dx.doi.org/10.1155/2017/1975902 |
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