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

我们之前的研究表明，通过设计一种融合的病毒膜糖蛋白复合体可以实现抗体靶向的细胞融合。单链抗体显示在麻疹血凝素(H)蛋白的胞外C末端，并引入点突变组合来消除其通过天然病毒受体CD46和SLAM触发融合的能力。当与麻疹融合蛋白(F)共表达时，重定向H蛋白(HaALS-scFv)可介导受体阴性或受体阳性的指标细胞与受体阳性的靶细胞的抗体靶向融合。现在，我们已经成功地用糖蛋白Haals-scFv和F作为靶向细胞进入的假类型慢病毒载体。因此，使用单链抗体进行靶向可能使我们能够将病毒重新定向到任何选定的细胞受体。我们还尝试利用肿瘤特异性单链抗体的鉴定技术来开发慢病毒展示的单链抗体文库。

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.