Efficient transduction of dendritic cells and induction of a T-cell response by third-generation lentivectors.
In order to induce a therapeutic T lymphocyte response, recombinant viral vaccines are designed to target professional antigen-presenting cells (APC) such as dendritic cells (DC). A key requirement for their use in humans is safe and efficient gene delivery. The present study assesses third-generation lentivectors with respect to their ability to transduce human and mouse DC and to induce antigen-specific CD8+ T-cell responses. We demonstrate that third-generation lentivectors transduce DC with a superior efficiency compared to adenovectors. The transfer of DC transduced with a recombinant lentivector encoding an antigenic epitope resulted in a strong specific CD8+ T-cell response in mice. The occurrence of lower proportions of nonspecifically activated CD8+ cells suggests a lower antivector immunity of lentivector compared to adenovector. Thus, lentivectors, in addition to their promise for gene therapy of brain disorders might also be suitable for immunotherapy.
Esslinger
Christoph
C
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland.
Romero
Pedro
P
MacDonald
H Robson
HR
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic
D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma