Specific cell targeting for delivery of toxins into small-cell lung cancer using a streptavidin fusion protein complex.
New modalities of treatment for small-cell lung cancer (SCLC) are needed, because the majority of patients continue to die of disseminated disease despite an initial response to conventional chemotherapy. Abnormal surface expression of the neural-cell adhesion molecule (NCAM) has been noted to be highly associated with SCLC. We examined the ability and efficiency of a streptavidin-Protein A (ST-PA) fusion protein complexed with an anti-NCAM monoclonal 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 internalized and exhibited beta-galactosidase activity. In addition, we evaluated cytotoxic activity against SCLC lines NCI-H69 and NCI-H526 by efficient delivery of biotinylated glucose oxidase using the same ST-PA/anti-NCAM Mab 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 unique surface molecules (antigens) using the corresponding Mab/ST-PA complex to transfer a variety of effector molecules; e.g., immunotoxic compounds, into target cells with a high degree of efficiency and specificity.
Yu
A
A
Department of Medicine, New York University School of Medicine, and Chest Service, Bellevue Hospital Center, New York, USA.
Choi
J
J
Ohno
K
K
Levin
B
B
Rom
W N
WN
Meruelo
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D001710:Biotin / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002452:Cell Count; D002470:Cell Survival; D018014:Gene Transfer Techniques; D005949:Glucose Oxidase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D019809:Streptavidin / Q000235:genetics*; D014118:Toxins, Biological / Q000235:genetics*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics
D000911:Antibodies, Monoclonal; D019006:Neural Cell Adhesion Molecules; D011993:Recombinant Fusion Proteins; D014118:Toxins, Biological; D001710:Biotin; D019809:Streptavidin; D005949:Glucose Oxidase; D001616:beta-Galactosidase