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Toxicity Profile of the Investigational New Biotherapeutic Agent, B43 (Anti-CD 19)-Pokeweed Antiviral Protein Immunotoxin

1996; Taylor & Francis; Volume: 22; Issue: 1-2 Linguagem: Inglês

10.3109/10428199609051729

1042-8194

Roland Günther, Lisa M. Chelstrom, Heather Wendorf, Elizabeth Schneider, Kristi Covalciuc, Bradley K. Johnson, Dina Clementson, J D Irvin, Dorothea E. Myers, Fatih M. Uckun,

Acute Lymphoblastic Leukemia research

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 un-conjugated 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.