Toxicity profile of the investigational new biotherapeutic agent, B43 (anti-CD19)-pokeweed antiviral protein immunotoxin

被引：8

作者：

Gunther, R ^{[1
]}

Chelstrom, LM ^{[1
]}

Wendorf, HR ^{[1
]}

Schneider, EA ^{[1
]}

Covalciuc, K ^{[1
]}

Johnson, B ^{[1
]}

Clementson, D ^{[1
]}

Irvin, JD ^{[1
]}

Myers, DE ^{[1
]}

Uckun, FM ^{[1
]}

机构：

[1] UNIV MINNESOTA, BIOTHERAPY PROGRAM, ROSEVILLE, NSW, AUSTRALIA

来源：

LEUKEMIA & LYMPHOMA | 1996年 / 22卷 / 1-2期

关键词：

leukemia; immunotoxin; biotherapy;

D O I：

10.3109/10428199609051729

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：61 / +

页数：1

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