Abstract
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 ratios. This heterogeneity makes it impossible to precisely deliver a predetermined immunotoxin dose to target cells and impairs the accuracy of pharmacologic studies. In this report, we describe the preparation and 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. Compared to the 180 kDa immunotoxin, the 210 kDa immunotoxin displayed greater in vitro chemical stability, resulted in higher systemic exposure levels in vivo, and was a more effective anti-leukemic agent in a SCID 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 against relapsed B-lineage ALL.
References
Mar 1, 1979·Computer Programs in Biomedicine·D Z D'Argenio, A Schumitzky
Jan 1, 1992·Pharmacology & Therapeutics·J D Irvin, F M Uckun
Feb 15, 1991·Journal of Immunological Methods·D E MyersF M Uckun
Dec 1, 1989·Transplantation·K A ReimannN L Letvin
Jan 1, 1988·The American Journal of Pediatric Hematology/oncology·P S GaynonG D Hammond
Aug 1, 1988·Pediatric Clinics of North America·D G Poplack, G Reaman
Aug 20, 1987·The New England Journal of Medicine·J H KerseyB Bostrom
Jan 1, 1986·Medical and Pediatric Oncology·W A BleyerG D Hammond
Feb 1, 1986·The Journal of Experimental Medicine·F M UckunD A Vallera
May 1, 1986·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·P G SteinherzH Sather
Dec 5, 1986·Cell·I PastanD J FitzGerald
Apr 1, 1993·Leukemia & Lymphoma·F M UckunL L Houston
Nov 1, 1993·British Journal of Haematology·F M Uckun
Oct 28, 1993·The New England Journal of Medicine·G K RiveraW M Crist
Oct 28, 1993·The New England Journal of Medicine·F M UckunN K Ramsay
Citations
Oct 16, 1996·Journal of Immunological Methods·D A ValleraJ H Kersey
Dec 24, 1997·Immunopharmacology·R Baluna, E S Vitetta
Feb 24, 2005·BMC Infectious Diseases·Fatih M UckunAlexander S Petkevich
Dec 24, 1997·Leukemia & Lymphoma·D E MyersF M Uckun
Jun 1, 1996·Leukemia & Lymphoma·R GuntherF M Uckun
Jun 25, 2016·Toxins·Massimo BortolottiLetizia Polito