Toxicity and immunogenicity of monoclonal antimelanoma antibody-ricin A chain immunotoxin in rats.
This study was performed to assess the subacute toxicity and immunogenicity in rats of XOMAZYME-MEL, an antimelanoma monoclonal antibody-ricin A chain immunotoxin. Female Sprague-Dawley rats received 14 consecutive daily i.v. injections of XOMAZYME-MEL at doses of 5 mg/kg/day, 1 mg/kg/day, or normal saline. Animals from each dose group were sacrificed on days 8, 15, and 22. The low dose of immunotoxin was well tolerated and produced only minimal signs of toxicity. Side effects in animals receiving the high dose of immunotoxin consisted of transient weight loss, peripheral edema, leukocytosis, hypoalbuminemia, and mildly elevated liver function tests. Histological findings in these animals included cytoplasmic vacuolization of hepatocytes, focal myocardial and skeletal muscle degeneration, and renal deposits of proteinaceous casts. The administration of immunotoxin resulted in the appearance of anti-mouse and antiricin A chain immunoglobulin binding activity in the sera of treated animals. This study documents the systemic effect of the multiple-dose administration of a ricin A chain immunotoxin in rats.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology; D005260:Female; D000922:Immunotoxins / Q000009:adverse effects* / Q000276:immunology; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D008545:Melanoma / Q000276:immunology*; D009132:Muscles / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin / Q000276:immunology / Q000633:toxicity*; D012709:Serum Albumin / Q000032:analysis
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012709:Serum Albumin; C059257:XomaZyme; D012276:Ricin