Gunther R, Chelstrom L M, Wendorf H R, Schneider E A, Covalciuc K, Johnson B, Clementson D, Irvin J D, Myers D E, Uckun F M
University of Minnesota Biotherapy Program, Roseville 55113, USA.
Leuk Lymphoma. 1996 Jun;22(1-2):61-70, follow.186, color plate II-V. doi: 10.3109/10428199609051729.
The investigational biotherapeutic agent, B43(anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin, has shown substantial anti-leukemic activity in SCID mouse models of human B-lineage leukemia and lymphoma. In this report, we describe the results of a comprehensive preclinical toxicity study which determined the toxicity profile of B43-PAP in BALB/c mice. Administration of unconjugated B43 monoclonal antibody was not associated with any toxicity, whereas B43-PAP caused dose-limiting and cardiac and renal toxicities which were fatal. In addition, B43-PAP also caused multifocal skeletal myofiber necrosis, which was associated with abnormal gait and lethargy. Notably, parenteral administrations of methylprednisolone, pentoxyphylline, or dopamine were able to markedly reduce B43-PAP related toxicity. This study provides a basis for further evaluation of the toxicity of B43-PAP in monkeys and humans.
