TOXICITY PROFILE OF THE INVESTIGATIONAL NEW BIOTHERAPEUTIC AGENT, B43(ANTI-CD19)-POKEWEED ANTIVIRAL PROTEIN IMMUNOTOXIN

The investigational biotherapeutic agent, B43(anti-CD19)-pokeweed anti viral protein (PAP) immunotoxin, has shown substantial anti-leukemic a ctivity in SCID mouse models of human B-lineage leukemia and lymphoma. In this report, we describe the results of a comprehensive preclinica l toxicity study which determined the toxicity profile of B43-PAP in B ALB/c mice. Administration of unconjugated B43 monoclonal antibody was not associated with any toxicity, whereas B43-PAP caused dose-limitin g and cardiac and renal toxicities which were fatal. In addition, B43- PAP also caused multifocal skeletal myofiber necrosis, which was assoc iated with abnormal gait and lethargy. Notably, parenteral administrat ions 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 human s.