A conjugate of adriamycin and monoclonal antibodies to Thy-1 antigen inhibits human neuroblastoma cells in vitro.
Antibodies to the differentation antigen Thy-1 were linked via a dextran-hydrazide bridge to adriamycin. These monoclonal antibodies, which were previously prepared against first-trimester human fetal cells, reacted with several human brain tissue tumors such as neuroblastoma, glioma, and leiomyosarcoma through a common differentiation antigen, Thy-1. The conjugates were tested in vitro for their cytotoxic effects on a neuroblastoma cell line LA-N-I. The conjugate maintained its full drug and antibody activities. Moreover, the specific conjugate exhibited a higher efficacy in inhibition of RNA synthesis and was more cytotoxic than the nonspecific Ig-drug conjugate. Fluorescent microscopy showed that the specific conjugate was able to penetrate the cell membrane. Both the specific antibody and the drug were also observed to accumulate in the cell nucleus. Flow microfluorometric analysis of cellular DNA traverse showed that the specific antibody-drug conjugate caused a higher accumulation of neuroblastoma cells in stage G2 of the cell cycle than did the free drug, perhaps indicating a more efficient prevention of the progression of cells through mitosis.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000188:drug therapy* / Q000276:immunology; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018800:Thy-1 Antigens; D004317:Doxorubicin