TARGETED GENE DELIVERY TO KAPOSIS-SARCOMA CELLS VIA THE FIBROBLAST GROWTH-FACTOR RECEPTOR

Kaposi's sarcoma (KS) is a major AIDS-related malignancy associated wi th significant morbidity and mortality, Current chemotherapeutic regim ens are associated with a dismal prognosis, In an effort to develop a new approach to KS treatment, we devised a gene therapy-based adenovir us retargeting schema that redirects the adenovirus to fibroblast grow th factor receptors endogenously present on the cell surface of KS cel ls. By using a bifunctional conjugate consisting of a blocking antiade noviral knob Fab linked to basic fibroblast growth factor, FGF2, the g ene transduction of KS cells was enhanced 7.7-44 fold; recombinant ade noviruses encoding either the firefly luciferase reporter gene, or the herpes simplex thymidine kinase gene, demonstrated quantitative enhan cement of expression in the KS cell lines, In this regard, two KS cell lines that were previously refractory to native adenovirus transducti on could be successfully transduced by the addition of the conjugate, This study thus addresses the utility of adenoviral retargeting to the FGF receptor in KS cells that are ordinarily transduction refractory to standardized approaches and allows practical development of gene th erapy approaches for the treatment of human KS.