Ledermann J A, Begent R H, Bagshawe K D
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Br J Cancer. 1988 Nov;58(5):562-6. doi: 10.1038/bjc.1988.259.
Repeated therapy of cancer with mouse monoclonal antibodies frequently produces antibodies directed against the administered antibody. We have investigated the ability of cyclosporin A (CsA) and the use of ultracentrifuged antibody to prevent the formation of anti-antibodies in rabbits. Courses of CsA, 20 mgkg-1 day-1, were given intramuscularly for 6 days to rabbits and a mouse monoclonal anti-human chorionic gonadotrophin antibody was given intravenously on day 2 with or without ultracentrifugation to remove microaggregates. The whole course was repeated after an interval of two weeks. Rabbit anti-mouse antibody production was prevented in all 8 animals that were given CsA and ultracentrifuged preparation (non UC-W14). Anti-mouse antibody was produced by all the animals that were not given CsA. A further dose of mouse antibody eight weeks after CsA demonstrated that immunological recovery had occurred in all four animals re-challenged with non UC-W14 but only 3/7 animals given an UC-W14 preparation. This suggests that CsA and ultracentrifugation facilitate the induction of immunological tolerance. The complete suppression of antibody production which could be achieved justifies a clinical trial of CsA and ultracentrifugation of antibody.
用小鼠单克隆抗体反复治疗癌症时，常常会产生针对所施用抗体的抗体。我们研究了环孢素A（CsA）的作用以及使用超速离心抗体来防止兔体内抗抗体形成的情况。给兔肌肉注射剂量为20mg/kg/天的CsA，持续6天，并在第2天静脉注射小鼠抗人绒毛膜促性腺激素单克隆抗体，抗体进行或不进行超速离心以去除微聚体。间隔两周后重复整个疗程。在所有8只接受CsA和超速离心制剂（非UC-W14）的动物中，兔抗小鼠抗体的产生得到了预防。所有未接受CsA的动物都产生了抗小鼠抗体。在CsA治疗八周后再给予一剂小鼠抗体，结果显示，在用非UC-W14制剂再次激发的所有4只动物中都出现了免疫恢复，但在给予UC-W14制剂的动物中，只有3/7出现了免疫恢复。这表明CsA和超速离心有助于诱导免疫耐受。能够实现的抗体产生的完全抑制证明了对CsA和抗体超速离心进行临床试验是合理的。
