Stoudemire J B, Mischak R, Foxall C, Harkonen W S, Del Rio M, Spitler L E
Xoma Corporation, Berkeley, California.
Mol Biother. 1990 Sep;2(3):179-84.
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)
我们开展了一项研究，以确定用环磷酰胺（CY）治疗是否能抑制用鼠单克隆抗体-蓖麻毒蛋白A链免疫毒素（IT）处理的大鼠体内抗鼠抗体和抗蓖麻毒蛋白A链抗体的形成。雌性斯普拉格-道利大鼠静脉注射剂量为5 mg/kg体重的IT，单独给药或与剂量水平为10或20 mg/kg体重的CY联合给药。IT以一个疗程或两个疗程给药，每个疗程包括连续5天静脉注射（研究的第0至4天，或第0至4天以及第21至25天）。环磷酰胺在研究的第2、4、6、13和17天给予接受单疗程IT的组；接受两个疗程IT的组在第23、25和27天额外给予CY剂量。在第4、14、21、28和35天，评估每组动物的抗鼠IgG和蓖麻毒蛋白A链抗体，以及临床实验室参数和组织病理学。单独接受IT的动物产生了显著滴度的抗鼠抗体和抗蓖麻毒蛋白A链抗体。与接受单疗程IT的动物的反应相比，接受第二疗程IT的动物在第28天和35天对IT两种成分的反应显著增强。与单独接受IT的组相比，接受一个或两个疗程CY与IT联合治疗的组对鼠IgG和蓖麻毒蛋白A链的抗体反应均显著降低。（摘要截短至250字）
