Development of tumor-targeted therapy using lentivirus-displayed antibody library

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We previously showed that antibody-targeted cell fusion can be achieved by engineering a fusogenic viral membrane glycoprotein complex. Single-chain antibodies were displayed at the extracellular C terminus of the measles hemagglutinin (H) protein, and combinations of point mutations were introduced to ablate its ability to trigger fusion through the native viral receptors CD46 and SLAM. When coexpressed with the measles fusion (F) protein, the retargeted H proteins (Haals-scFvs) could mediate antibody-targeted cell fusion of receptor-negative or receptor-positive index cells with receptor-positive target cells. Now we have successfully pseudotyped lentiviral vectors with the glycoproteins Haals-scFv and F for targeted cell entry. Thus, the use of single chain antibodies for targeting potentially allows us to redirect the virus against any chosen cellular receptor. We also try to develop lentivirus-displayed scFvs library using the technology for identification of tumor-specific scFv.