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.