Efficient gene transfer to human peripheral blood monocyte-derived dendritic cells using human immunodeficiency virus type 1-based lentiviral vectors

Détails

ID Serval
serval:BIB_BEA371CC0949
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Efficient gene transfer to human peripheral blood monocyte-derived dendritic cells using human immunodeficiency virus type 1-based lentiviral vectors
Périodique
Hum Gene Ther
Auteur(s)
Chinnasamy N., Chinnasamy D., Toso J. F., Lapointe R., Candotti F., Morgan R. A., Hwu P.
ISSN
1043-0342 (Print)
ISSN-L
1043-0342
Statut éditorial
Publié
Date de publication
2000
Volume
11
Numéro
13
Pages
1901-9
Langue
anglais
Notes
Chinnasamy, N
Chinnasamy, D
Toso, J F
Lapointe, R
Candotti, F
Morgan, R A
Hwu, P
eng
Hum Gene Ther. 2000 Sep 1;11(13):1901-9.
Résumé
Dendritic cells (DCs) are potent antigen-presenting cells and are capable of activating naive T cells. Gene transfer of tumor antigen and cytokine genes into DCs could be an important strategy for immunotherapeutic applications. Dendritic cells derived from peripheral blood monocytes do not divide and are therefore poor candidates for gene transfer by Moloney murine leukemia virus (Mo-MuLV)-based retroviral vectors. Lentiviral vectors are emerging as a powerful tool for gene delivery into dividing and nondividing cells. A three-plasmid expression system pseudotyped with the envelope from vesicular stomatitis virus (VSV-G) was used to generate lentiviral vector particles expressing enhanced green fluorescent protein (EGFP). Peripheral blood monocyte-derived DCs were cultured in the presence of GM-CSF and IL-4 and transduced with lentiviral or Mo-MuLV-based vectors expressing EGFP. FACS analysis of lentiviral vector-transduced DCs derived either from normal healthy volunteers or from melanoma patients demonstrated transduction efficiency ranging from 70 to 90% compared with 2-8% using Mo-MuLV-based vectors pseudotyped with VSV-G. Comparison of lentiviral vectors expressing EGFP driven by CMV or human PGK promoters showed similar levels of transgene expression. Lentiviral vector preparations produced in the absence of HIV accessory proteins transduced DCs at efficiencies equal to vectors produced with accessory proteins. Alu-HIV-1 LTR PCR demonstrated the genomic integration of the lentiviral vector in the transduced DCs. Transduced cells showed characteristic dendritic cell phenotype and strong allostimulatory capacity and maintained the ability to respond to activation signals such as CD40 ligand and lipopolysaccharide. These results provide evidence that lentiviral vectors are efficient tools for gene transfer and expression in monocyte-derived DCs that could be useful for immunotherapeutic applications.
Mots-clé
Alu Elements/genetics, Antigens, CD, Cytomegalovirus/genetics, Dendritic Cells/immunology/*physiology/virology, *Gene Transfer Techniques, Green Fluorescent Proteins, HIV-1/genetics, Humans, Immunoglobulins/metabolism, Interleukin-12/metabolism, Lentivirus/*genetics, Luminescent Proteins/genetics/metabolism, Melanoma/genetics/pathology, Membrane Glycoproteins/metabolism, Moloney murine leukemia virus/genetics, Monocytes/*cytology/virology, Promoter Regions, Genetic, T-Lymphocytes/immunology, Vesicular stomatitis Indiana virus/genetics, Viral Proteins/genetics
Pubmed
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
20/08/2019 16:32
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