FAVORABLE PHARMACODYNAMIC FEATURES AND SUPERIOR ANTILEUKEMIC ACTIVITYOF B43 (ANTI-CD19) IMMUNOTOXINS CONTAINING 2 POKEWEED ANTIVIRAL PROTEIN MOLECULES COVALENTLY-LINKED TO EACH MONOCLONAL-ANTIBODY MOLECULE

Standard immunotoxin production procedures using whole IgG as the MoAb moiety yield a heterogeneous mixture of 180 kDa, 210 kDa, and 240 kDa immunotoxin species with 1 to 1, 1 to 2, and 1 to 3 MoAb to toxin rat ios. This heterogeneity makes it impossible to precisely deliver a pre determined immunotoxin dose to target cells and impairs the accuracy o f pharmacologic studies. In this report, we describe the preparation a nd characterization of B43(anti-CD19)-pokeweed antiviral protein (PAP) immunotoxins containing either one or two 30 kDa PAP toxin molecules covalently linked to each 150 kDa B43 monoclonal antibody molecule, Co mpared to the 180 kDa immunotoxin, the 210 kDA immunotoxin displayed g reater in vitro chemical stability, resulted in higher systemic exposu re levels in vivo, and was a more effective anti-leukemic agent in a S CID mouse model of human B-lineage acute lymphoblastic leukemia. Taken together, the results of this study recommend the clinical evaluation of 210 kDa B43 -PAP as a potentially more effective immunotoxin again st relapsed B-lineage ALL.