Efficient transduction of healthy and malignant plasma cells by lentiviral vectors pseudotyped with measles virus glycoproteins.
A lot of genes deregulated in malignant plasma cells (PCs) involved in multiple myeloma have been reported these last years. The expression of some of these genes is associated with poor survival. A critical step is to elucidate the biological mechanisms triggered by these gene products. Such studies are hampered by the difficulty to obtain malignant PCs and to genetically modify them. Usual lentiviral vectors (LVs) pseudotyped with vesicular stomatitis virus envelope glycoprotein poorly transduced healthy and malignant PCs. Here, we report that LVs pseudotyped with the hemagglutinin and fusion glycoproteins from the measles Edmonston strain (H/F-LVs) can efficiently and stably transduce healthy and primary malignant PCs, without modifying their main phenotypic characteristics. Both LV pseudotypes efficiently transduced human myeloma cell lines. Importantly, both healthy and malignant PCs expressed CD46 and SLAMF1/CD150 membrane proteins, which are critical receptors for binding and productive genetic modification by H/F-LVs. The ability to efficiently introduce and express a given gene into PCs opens the possibility to study in detail PC biology.
INSERM U1040, Institute for Research in Biotherapy, CHU Montpellier, Hospital St Eloi, Montpellier, France.
M
M
Schoenhals
C
C
Frecha
A
A
Bruyer
A
A
Caraux
J L
JL
Veyrune
M
M
Jourdan
J
J
Moreaux
F-L
FL
Cosset
E
E
Verhoeyen
B
B
Klein
D015703:Antigens, CD; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D016086:Lentivirus / Q000235:genetics*; D008459:Measles virus / Q000235:genetics*; D051916:Membrane Cofactor Protein; D009101:Multiple Myeloma / Q000235:genetics* / Q000628:therapy*; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics
D015703:Antigens, CD; D006023:Glycoproteins; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D014759:Viral Envelope Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1