CELL-SPECIFIC, MULTIDRUG DELIVERY SYSTEM USING STREPTAVIDIN PROTEIN-AFUSION PROTEIN

Tissue-specific delivery of variety of molecules has been a valuable t echnique for biological and medical research and for the diagnosis and therapy of cancer. We have therefore examined the ability of streptav idin-protein A (ST-PA) fusion protein complexed with monoclonal antibo dies (mAbs) to transfer biotinylated proteins into specific type of ce lls. ST-PA/mAbs complexes could efficiently deliver biotinylated beta- galactosidase into a variety of cancer cell lines through molecules ex pressed on their surface. In addition, ST-PA/mAb complexed with either biotinylated glucose oxidase or biotinylated ribonuclease A could be transferred to specific cell types and made to display cytotoxic activ ity against the transduced cell. The flexibility of the system was enh anced by the fact that the cell-targeting specificity could be altered by just changing the mAb used and the ''payload'' molecule could be r eplaced by substituting one biotinylated protein or enzyme with anothe r. This flexibility was achieved without the need to generate a covale nt chemical link or engineering new recombinant molecules. Results obt ained to date suggest that the ST-PA fusion protein may be used as a n early ''universal carrier'' to transfer a variety of effector molecule s into target cells with a high degree of specificity. Essentially, th e ST-PA fusion protein effectively serves as a high-efficiency, modula r ''molecular bridge'' for the transfer into cells of a wide variety o f effector molecules. (C) 1996 Academic Press, Inc.