D A Vallera, L J Burns, A E Frankel, A R Sicheneder, R Gunther, K Gajl-Peczalska, C A Pennell, J H Kersey
An immunotoxin consisting of a monoclonal antibody specific for CD7, a cell surface determinant expressed on T acute lymphocytic leukemia (T-ALL) blast cells, was linked to the potent plant toxin deglycosylated ricin toxin A chain (dgRTA) and is currently under evaluation in phase I clinical trials. Scale-up production of this immunotoxin, called DA7, was simplified using a two-step purification protocol that resulted in a highly purified immunotoxin meeting FDA criteria for IND approval. The anti-CD7 antibody, 3Ale, an IgG2b, was coupled to toxin using two different heterobifunctional cross-linkers, (1) N-succinimidyl-3-(2-pyridyl-dithiolproprionate) (SPDP), considered a standard croslinker and (2) 4-succinimidyloxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio)tolu ene (SMPT), designed to hinder the in vivo breakdown of the toxin/antibody disulfide bond...
October 16, 1996: Journal of Immunological Methods