Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors.
Up to now, no lentiviral vector (LV) tool existed to govern efficient and stable gene delivery into quiescent B lymphocytes, which hampers its application in gene therapy and immunotherapy areas. Here, we report that LVs incorporating measles virus (MV) glycoproteins, H and F, on their surface allowed transduction of 50% of quiescent B cells, which are not permissive to VSVG-LV transduction. This high transduction level correlated with B-cell SLAM expression and was not at cost of cell-cycle entry or B-cell activation. Moreover, the naive and memory phenotypes of transduced resting B cells were maintained. Importantly, H/F-LVs represent the first tool permitting stable transduction of leukemic cancer cells, B-cell chronic lymphocytic leukemia cells, blocked in G(0)/G(1) early phase of the cell cycle. Thus, H/F-LV transduction overcomes the limitations of current LVs by making B cell-based gene therapy and immunotherapy applications feasible. These new LVs will facilitate antibody production and the study of gene functions in these healthy and cancer immune cells.
Frecha
Cecilia
C
Inserm U758, Human Virology Department, Université de Lyon, Ecole Normale Supérieure de Lyon, Lyon, France.
Costa
Caroline
C
Lévy
Camille
C
Nègre
Didier
D
Russell
Stephen J
SJ
Maisner
Andrea
A
Salles
Gilles
G
Peng
Kah-Whye
KW
Cosset
Francois-Loïc
FL
Verhoeyen
Els
E
D015703:Antigens, CD / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D005260:Female; D016193:G1 Phase; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D008213:Lymphocyte Activation; D008297:Male; D008459:Measles virus; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D016192:Resting Phase, Cell Cycle; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014161:Transduction, Genetic / Q000379:methods*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D006023:Glycoproteins; D011956:Receptors, Cell Surface; D014760:Viral Fusion Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1