The effects of cyclophosphamide on the toxicity and immunogenicity of ricin A chain immunotoxin in rats.
We conducted a study to determine if treatment with cyclophosphamide (CY) could suppress the formation of anti-murine and anti-ricin A chain antibodies in rats treated with a murine monoclonal antibody-ricin A chain immunotoxin (IT). Female Sprague-Dawley rats received intravenous doses of IT at a dose of 5 mg/kg body weight alone or in combination with CY at a dose level of either 10 or 20 mg/kg body weight. The IT was given as one or two courses consisting of five consecutive daily intravenous injections (days 0 to 4, or days 0 to 4 and days 21 to 25 of the study). Cyclophosphamide was given on days 2, 4, 6, 13, and 17 of the study to the group receiving a single course of IT; additional doses of CY were administered on days 23, 25, and 27 to the group receiving two courses of IT. On days 4, 14, 21, 28, and 35, animals from each group were evaluated for antibodies to murine IgG and ricin A chain, and for clinical laboratory parameters and histopathology. Animals receiving IT alone developed significant titers of both anti-murine and anti-ricin A chain antibodies. Compared with the response in the animals receiving single-course IT, the response to both of the components of the IT was significantly increased on days 28 and 35 in the animals receiving a second course of IT. The groups receiving a combination of either one or two courses of CY and IT demonstrated a significantly decreased antibody response to both the murine IgG and the ricin A chain compared with the group receiving IT alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Stoudemire
J B
JB
Xoma Corporation, Berkeley, California.
Mischak
R
R
Foxall
C
C
Harkonen
W S
WS
Del Rio
M
M
Spitler
L E
LE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D000922:Immunotoxins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D003520:Cyclophosphamide; D012276:Ricin