Specific cell targeting for delivery of toxins into small-cell lung cancerusing a streptavidin fusion protein complex

New modalities of treatment for small-cell lung cancer (SCLC) are needed, b ecause the majority of patients continue to die of disseminated disease des pite an initial response to conventional chemotherapy, Abnormal surface exp ression of the neural-cell adhesion molecule (NCAM) has been noted to be hi ghly associated with SCLC. We examined the ability and efficiency of a stre ptavidin-Protein A (ST-PA) fusion protein complexed with an anti-NCAM monoc lonal antibody (Mab) to transfer biotinylated beta-galactosidase into human SCLC cell lines NCI-H69, NCI-H526, and NCI-H446, When the surface molecule NCAM was targeted with this system, more than 99% of the targeted cells in ternalized and exhibited beta-galactosidase activity. In addition, we evalu ated cytotoxic activity against SCLC lines NCI-H69 and NCI-H526 by efficien t delivery of biotinylated glucose oxidase using the same ST-PA/anti-NCAM M ab complex, Cytotoxicity of the transduced cells (SCLC) was 10-fold and 100 -fold greater, respectively, than the glucose oxidase control. This system could be widely applied for specific therapy of cancer cells by targeting u nique surface molecules (antigens) using the corresponding Mab/ST-PA comple x to transfer a variety of effector molecules; e.g., immunotoxic compounds, into target cells with a high degree of efficiency and specificity.