Lentiviral vectors and transduction of human cancer B cells.

摘要

A recent article by Hazan-Halevy et al assessed down-regulation of STAT3 in B-CLL cells (B-CLLs) using VSV-G pseudotyped lentiviral vectors (VSV-G-LVs) encoding for STAT3-small hairpin RNA (shRNA). They reported a transduction of 40% to 70% with VSV-G-LVs in nonstimulated B-CLLs. This is in sharp contrast with our recently published data demonstrating that VSV-G-LVs are not suited for efficient transduction of malignant B cells. Indeed, 4 independent laboratories reported that human B cells, even upon a proliferative stimulus, are highly refractory to VSV-G-LV-mediated gene transfer. We confirmed that even upon BCR stimulation, B-CLLs were not efficiently transduced by VSV-G-LVs as reported earlier by Bovia et al.2 Of high importance, we engineered a new generation of LVs carrying at their surface glycoproteins of the measles virus, H and F (H/F-LVs). These new LV-pseudotypes allowed very efficient gene transfer in resting T and B cells as well as in B-CLLs, whereas VSV-G-LVs failed, even at high vector doses.