Lowder J N, Miller R A, Hoppe R, Levy R
J Immunol. 1987 Jan 15;138(2):401-6.
Murine monoclonal antibodies stimulate the production of human anti-mouse immunoglobulin antibodies (AMIA) when administered to patients. This limits their long-term usefulness as therapeutic and diagnostic agents. We report the use of three maneuvers to suppress AMIA against T cell-specific monoclonal antibodies in cynomolgus monkeys. Twelve monkeys received daily i.v. infusions of 1 mg each of anti-Leu-2a, -3a, and -5 on days 1 through 10. One group (control) received no suppressive regimen. The second group received cyclosporine, 12.5 mg/kg daily on days -7 to +14. The third group (PI) were passively immunized with 0.4 ml of hyperimmune monkey AMIA serum on days -7, -1, 2, 4, 6, and 8. The fourth group (TLI) received 1700 rad fractionated total lymphoid irradiation ending on day -1. The animals treated with TLI were markedly delayed in the onset of AMIA, which was suppressed to less than 1% of the control group. The AMIA specific for the constant region of animals receiving PI was also suppressed to one-third of control. The majority of the AMIA in all the animals was anti-idiotypic and wholly anti-idiotypic in the TLI animals.
当给患者使用鼠单克隆抗体时，会刺激人体产生抗鼠免疫球蛋白抗体（AMIA）。这限制了它们作为治疗和诊断试剂的长期效用。我们报告了在食蟹猴中使用三种方法来抑制针对T细胞特异性单克隆抗体的AMIA。12只猴子在第1天至第10天每天静脉注射1毫克抗Leu - 2a、- 3a和- 5。一组（对照组）未接受抑制方案。第二组在第- 7天至+ 14天每天接受12.5毫克/千克的环孢素。第三组（PI）在第- 7天、- 1天、第2天、第4天、第6天和第8天用0.4毫升超免疫猴AMIA血清进行被动免疫。第四组（TLI）在第- 1天结束时接受1700拉德分次全身淋巴照射。接受TLI治疗的动物AMIA的出现明显延迟，被抑制到对照组的不到1%。接受PI的动物针对恒定区的AMIA也被抑制到对照组的三分之一。所有动物中的大多数AMIA是抗独特型的，而在TLI动物中完全是抗独特型的。
