Cyclosporin A prevents the anti-murine antibody response to a monoclonal anti-tumour antibody in rabbits

Abstract

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.