Effect of cyclophosphamide on the immunogenicity of monoclonal antimelanoma antibody-ricin A chain immunotoxin in rats.
This study was performed to determine the effect of treatment with cyclophosphamide (CY) on the formation of antimurine and anti-ricin A chain antibodies in rats treated with a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (IT). Animals received treatment with either IT alone or IT plus CY. IT treatment consisted of daily IV injections at a dose of 1 mg/kg/day on days 0, 1, 2, 3, 4. CY treatment consisted of a 25 mg/kg IP dose on day -1 followed by daily IP doses of 5 mg/kg/day on days 0, 1, 2, 3, 4. Antibody binding activities in treated animals were measured by enzyme-linked immunosorbent assay and reported as optical density values. Rats treated with IT plus CY had lower binding activity on day 7 (0.09 vs 0.6; p = .02), day 14 (0.42 vs 1.22; p = .001), and day 21 (0.11 vs 1.3; p = .001) compared to rats treated with IT alone. Lower levels of anti-ricin A chain binding activity were observed in CY treated rats on day 14 (0.35 vs 1.25; p = .001), but not on day 7 or day 21. These results indicate that treatment with CY can abrogate the immune response to murine antibody and partially abrogate the immune response to ricin A chain.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G; D000922:Immunotoxins / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin / Q000008:administration & dosage / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000922:Immunotoxins; D003520:Cyclophosphamide; D012276:Ricin