|
Title
|
|
|
|
Characterization of interleukin-15-transpresenting dendritic cells for clinical use
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| 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. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Journal of Immunology Research
| |
|
Publication
|
|
|
|
2017
| |
|
ISSN
|
|
|
|
2314-8861
2314-7156
| |
|
DOI
|
|
|
|
10.1155/2017/1975902
| |
|
Volume/pages
|
|
|
|
(2017)
, 8 p.
| |
|
Article Reference
|
|
|
|
1975902
| |
|
ISI
|
|
|
|
000405350700001
| |
|
Medium
|
|
|
|
E-only publicatie
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|