GENE THERAPY-BASED APPROACHES TO THE TREATMENT OF CANCER - DEVELOPMENT OF TARGETABLE RETROVIRAL VECTORS

The potential usefulness of retroviral vectors in cancer gene therapy would be dramatically increased if means could be developed to safely and efficiently target retroviruses to specific cell types in vivo. As a first step toward addressing this problem, we have developed geneti cally engineered retroviral vectors in which the Ligand binding portio n of the retroviral envelope glycoprotein is fused in-frame to the ext racellular domain of a murine Pc receptor. Preliminary studies have co nfirmed that retroviral vectors expressing this chimeric envelope prot ein can be targeted to particular eel types using monoclonal antibodie s. Currently, these vectors are being used to screen panels of monoclo nal antibodies raised against vascular endothelial cells in order to i dentify differentially expressed cell surface molecules that can act a s appropriate receptors for retroviral uptake and expression.