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Lentiviral-Vector-Based Dendritic Cell Vaccine Synergizes with Checkpoint Blockade to Clear Chronic Viral Infection.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2020 Aug 05; Vol. 28 (8), pp. 1795-1805. Date of Electronic Publication: 2020 May 20. - Publication Year :
- 2020
-
Abstract
- Dendritic cell vaccines are a promising strategy for the treatment of cancer and infectious diseases but have met with mixed success. We report on a lentiviral vector-based dendritic cell vaccine strategy that generates a cluster of differentiation 8 (CD8) T cell response that is much stronger than that achieved by standard peptide-pulsing approaches. The strategy was tested in the mouse lymphocytic choriomeningitis virus (LCMV) model. Bone marrow-derived dendritic cells from SAMHD1 knockout mice were transduced with a lentiviral vector expressing the GP33 major-histocompatibility-complex (MHC)-class-I-restricted peptide epitope and CD40 ligand (CD40L) and injected into wild-type mice. The mice were highly protected against acute and chronic variant CL-13 LCMVs, resulting in a 100-fold greater decrease than that achieved with peptide epitope-pulsed dendritic cells. Inclusion of an MHC-class-II-restricted epitope in the lentiviral vector further increased the CD8 T cell response and resulted in antigen-specific CD8 T cells that exhibited a phenotype associated with functional cytotoxic T cells. The vaccination synergized with checkpoint blockade to reduce the viral load of mice chronically infected with CL-13 to an undetectable level. The strategy improves upon current dendritic cell vaccine strategies; is applicable to the treatment of disease, including AIDS and cancer; and supports the utility of Vpx-containing vectors.<br /> (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biomarkers
Dendritic Cells virology
Disease Models, Animal
Disease Susceptibility
Histocompatibility Antigens Class II
Host-Pathogen Interactions immunology
Humans
Lymphocytic Choriomeningitis prevention & control
Lymphocytic choriomeningitis virus immunology
Mice
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
Viral Vaccines administration & dosage
Virus Diseases etiology
Virus Diseases immunology
Dendritic Cells drug effects
Dendritic Cells immunology
Genetic Vectors administration & dosage
Genetic Vectors genetics
Immune Checkpoint Inhibitors pharmacology
Lentivirus genetics
Viral Vaccines immunology
Virus Diseases prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 28
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 32497512
- Full Text :
- https://doi.org/10.1016/j.ymthe.2020.05.018