Myers D E, Yanishevski Y, Masson E, Irvin J D, Evans W E, Uckun F M
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis 55455, USA.
Leuk Lymphoma. 1995 Jun;18(1-2):93-102. doi: 10.3109/10428199509064928.
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.
使用完整IgG作为单克隆抗体部分的标准免疫毒素生产程序会产生180 kDa、210 kDa和240 kDa免疫毒素种类的异质混合物，单克隆抗体与毒素的比例分别为1比1、1比2和1比3。这种异质性使得无法精确地向靶细胞递送预定剂量的免疫毒素，并损害了药理学研究的准确性。在本报告中，我们描述了B43（抗CD19）-商陆抗病毒蛋白（PAP）免疫毒素的制备和特性，该免疫毒素含有一个或两个30 kDa的PAP毒素分子，它们与每个150 kDa的B43单克隆抗体分子共价连接。与180 kDa免疫毒素相比，210 kDa免疫毒素在体外显示出更高的化学稳定性，在体内导致更高的全身暴露水平，并且在人B系急性淋巴细胞白血病的SCID小鼠模型中是一种更有效的抗白血病药物。综上所述，本研究结果建议对210 kDa B43-PAP进行临床评估，作为一种可能对复发的B系急性淋巴细胞白血病更有效的免疫毒素。
