| Toxicologic evaluations of an immunotoxin, H65-RTA. | |
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MedLine Citation:
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PMID: 7657064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of acute and multiple dose toxicology studies were performed to support the clinical dose and to evaluate the systemic toxicity of an immunotoxin, H65-RTA. H65-RTA consists of a murine anti-CD5 monoclonal antibody and ricin A chain (RTA). The LD50 of H65-RTA was estimated to be between 60 and 62.5 mg/kg in the rat. H65-RTA was administered to the rat and the monkey as a bolus injection at doses of 0.1, 0.5, and 2 mg/kg and over 1-hr infusion at 0.2 and 2 mg/kg, respectively. Two to three weeks of postdosing recovery was included in the study design. Following repeated doses of H65-RTA, the following findings were demonstrated: peripheral edema, decreased body weight, decreased body temperature (monkey only) in addition to a general inflammatory reaction evidenced by changes in hematology, clinical chemistry, and urinalysis parameters. Histopathologically, chronic inflammation in the nonarticular soft tissue was found in the rat at doses of 0.1 mg/kg and higher and monkeys developed much more severe toxicity when compared to the rat at the same doses. Inflammation, hemorrhage, and/or edema were evident in a variety of tissues. Myeloid hyperplasia was also evident. Additional findings resulting from the drug-related stress involved adrenals, spleen, thymus, and lymph nodes. All toxicity was reversible. The antibody response was evident in rats at doses of 0.5 mg/kg and higher and in all monkeys at doses of 0.2 and 2 mg/kg. In conclusion, since H65 antibody does not cross-react with the T cells from either the rat or the cynomolgus monkey, the toxicity observed in the studies described above was not related to T lymphocytes and was probably due to a series of acute to subacute inflammatory reactions caused largely by the RTA moiety of H65-RTA. |
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Authors:
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A H Kung; J A Cavagnaro; A Makin; M A White; K N Kong |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Fundamental and applied toxicology : official journal of the Society of Toxicology Volume: 26 ISSN: 0272-0590 ISO Abbreviation: Fundam Appl Toxicol Publication Date: 1995 Jun |
Date Detail:
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Created Date: 1995-10-02 Completed Date: 1995-10-02 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 8200838 Medline TA: Fundam Appl Toxicol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 75-84 Citation Subset: IM |
Affiliation:
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XOMA Corporation, Berkeley, California 94710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / administration & dosage, toxicity* Antibody Formation Blood Cell Count Blood Chemical Analysis / veterinary Body Temperature Body Weight Female Immunotoxins / administration & dosage, toxicity* Inflammation / etiology Injections, Intravenous Macaca fascicularis Male Organ Size Rats Rats, Sprague-Dawley Ricin / administration & dosage, toxicity* Toxicity Tests Urinalysis / veterinary |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Immunotoxins; 141483-72-9/zolimomab aritox; 9009-86-3/Ricin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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