IMMUNOTOXIN THERAPY FOR PATIENTS WITH B CELL TUMORS

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The aim of this program project is to initiate clinical trials using ricin A chain-containing immunotoxins (A-IT). Anti-delta-A-IT will be administered intravenously to patients sIgD B cell lymphomas and leukemias. In subsequent clinical trials, lysosomotropic agents and B-chain IT will be used to potentiate A-IT targent cell toxicity. These studies will necessitate the preparation and characterization of large amounts of highly purified A and B chain, anti-delta antibody, anti-antibody and the resulting ITs. Using sensitive clonal assays, the ITs will be tested for potency in killing sIgD tumor cells in vitro, as well as, their nonspecific toxicity in rodents and primates. The primary goal of the initial trial will be to determine and solve the problems resulting from the use of these ITs. If the A-IT does not induce side effects, then subsequent phase II trials will be performed.