Internalization of monoclonal antibodies selected for immunotoxin activity against small-cell lung cancer.
Two hybridomas producing MOABs with anti-SCLC activity were selected for immunotoxin activity by an indirect screen and were twice cloned. Binding activity of the MOABs to SCLC cells was demonstrated by immunoperoxidase activity, which could be blocked by streptavidin. The MOABs mediated the internalization of a biotinylated Fab' anti-mouse Ig marker at 37 degrees C. Internalization of the biotinylated marker by the SCLC target cells resulted in protection of the marker from streptavidin-blocking. These results show that MOABs selected for immunotoxin activity against SCLC can mediate internalization of an antibody fragment with a mass about 50% greater than that of the toxin. MOABs selected for immunotoxin activity may be useful for delivering agents other than toxins to the inside of SCLC cells.
Weltman
J K
JK
Department of Medical Oncology, Rhode Island Hospital 02903.
Melucci
C L
CL
Chen
J
J
Davidson
A E
AE
D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D001426:Bacterial Proteins; D001667:Binding, Competitive; D015415:Biomarkers; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007124:Immunoenzyme Techniques; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D000922:Immunotoxins / Q000378:metabolism / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D019809:Streptavidin; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D015415:Biomarkers; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D019809:Streptavidin