title: Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors.
abstract: 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.
authors: Inserm U758, Human Virology Department, Université de Lyon, Ecole Normale Supérieure de Lyon, Lyon, France.
authors: Cecilia
authors: C
authors: Frecha
authors: Caroline
authors: C
authors: Costa
authors: Camille
authors: C
authors: Lévy
authors: Didier
authors: D
authors: Nègre
authors: Stephen J
authors: SJ
authors: Russell
authors: Andrea
authors: A
authors: Maisner
authors: Gilles
authors: G
authors: Salles
authors: Kah-Whye
authors: KW
authors: Peng
authors: Francois-Loïc
authors: FL
authors: Cosset
authors: Els
authors: E
authors: Verhoeyen
mesh_terms: 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*
chemical_list: D015703:Antigens, CD; D006023:Glycoproteins; D011956:Receptors, Cell Surface; D014760:Viral Fusion Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1