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Conjugates (immunotoxins) comprising ricin A-chain and monoclonal antibody 96.5, which is specific for human melanoma-associated antigen p97, inhibited protein synthesis and colony formation of cultured human melanoma cells that expressed more than 80,000 molecules of p97 per cell. Cells expressing fewer than 5,000 molecules of p97 were not killed. The(More)
The kinetics of cytotoxicity induced by ricin and a series of immunotoxins consisting of ricin A-chain coupled to antibodies against cell-surface antigens has been studied. The inhibition of protein synthesis in cells treated with immunotoxins or ricin occurs after a lag period. The rate of protein synthesis decreases according to a mono-exponential(More)
In recent years, antibody--ricin-A-chain immunotoxins have been investigated as anti-neoplastic agents. To achieve in vivo therapy it is necessary that the immunotoxin remains in circulation at a sufficiently high level for a sufficiently long time to allow binding to tumor cells to occur. Therefore, examination of the pharmacology of immunotoxins may(More)
Vacuole formation around the Golgi and immunotoxin enhancement induced by low doses of the ionophore monensin were inhibited by 50% human plasma (final concentration), whereas the lysosomal pH increase remained unaffected. Immunotoxin enhancement by the Ca2+ antagonist perhexiline was also inhibited by plasma. The inhibiting factor was present in different(More)
HLA-A and B antigens were determined in 112 patients with insulin-dependent juvenile onset diabetes mellitus, who could be subdivided into "non" and "high responder" to insulin. The data revealed a trend of an association of these diabetes subgroups with only one of the diabetes-associated antigens HLA-B8 and HLA-BW15 and indicated the existence of at least(More)
The preparation of immunotoxins, hybrid proteins formed by disulfide bonding an antibody and the A-chain of ricin, has been studied in detail. Optimal conditions, both for the modification of the antibody and the coupling reaction between the modified antibodies and the toxin subunit, have been determined. Conditions of time, temperature and stoichiometry(More)
The participation of immune reactions in the EMC virus induced diabetes of the mouse was studied by immunosuppression with 500 R sublethal X-irradiation or 120 mg/kg Asta 5122, a cyclophosphamide derivative. Average glucose levels after X-irradiation and infection remained normal, while virus, infected, otherwise untreated mice, had significantly higher(More)
Several attempts to attack tumours in experimental systems have been made using conjugates of chemotherapeutic agents or potent toxins with antibodies (immunotoxins). In vitro studies have been highly successful, showing target specificity of a high order in some cases. However, so far, such conjugates have been inadequate in vivo, probably for two main(More)
An immunotoxin (IT) formed by a specific antibody coupled to the ricin A chain was adsorbed on colloidal gold particles (IT-Au). Binding and internalization of IT-Au in human lymphoblastic CEM cells were studied using electron microscopy. IT-Au showed specific cytotoxic activity toward the target cells. After 1 h at 4 degrees C, IT-Au were linked diffusely(More)