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Dendritic cell-specific delivery of Flt3L by coronavirus vectors secures induction of therapeutic antitumor immunity.
- Source :
-
PloS one [PLoS One] 2013 Nov 28; Vol. 8 (11), pp. e81442. Date of Electronic Publication: 2013 Nov 28 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Efficacy of antitumor vaccination depends to a large extent on antigen targeting to dendritic cells (DCs). Here, we assessed antitumor immunity induced by attenuated coronavirus vectors which exclusively target DCs in vivo and express either lymphocyte- or DC-activating cytokines in combination with a GFP-tagged model antigen. Tracking of in vivo transduced DCs revealed that vectors encoding for Fms-like tyrosine kinase 3 ligand (Flt3L) exhibited a higher capacity to induce DC maturation compared to vectors delivering IL-2 or IL-15. Moreover, Flt3L vectors more efficiently induced tumor-specific CD8(+) T cells, expanded the epitope repertoire, and provided both prophylactic and therapeutic tumor immunity. In contrast, IL-2- or IL-15-encoding vectors showed a substantially lower efficacy in CD8(+) T cell priming and failed to protect the host once tumors had been established. Thus, specific in vivo targeting of DCs with coronavirus vectors in conjunction with appropriate conditioning of the microenvironment through Flt3L represents an efficient strategy for the generation of therapeutic antitumor immunity.
- Subjects :
- Animals
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines genetics
Cancer Vaccines immunology
Cell Line
Dendritic Cells immunology
Interleukin-15 genetics
Interleukin-15 immunology
Interleukin-2 genetics
Interleukin-2 immunology
Membrane Proteins immunology
Mice
Coronavirus genetics
Dendritic Cells metabolism
Genetic Vectors genetics
Immunotherapy methods
Membrane Proteins genetics
Neoplasms immunology
Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24312302
- Full Text :
- https://doi.org/10.1371/journal.pone.0081442