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

Roland Gunther University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Lisa M. Chelstrom University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Heather R. Wendorf University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Elizabeth A. Schneider University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Kristi Covalciuc University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Bradley Johnson University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Dina Clementson University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

James D. Irvin University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Dorothea E. Myers University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

Fatih M. Uckun University of Minnesota Biotherapy Program and the Centralized Immunotoxin Resource Laboratory of the Childrens Cancer Group, Roseville, Minnesota, Southwest Texas State University, San Marcos, TexasUSA

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Abstract

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.

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

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

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