Cyclosporin A prevents the anti-murine antibody response to a monoclonal anti-tumour antibody in rabbits.
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.
Ledermann
J A
JA
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Begent
R H
RH
Bagshawe
K D
KD
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D011817:Rabbits; D014461:Ultracentrifugation
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D007074:Immunoglobulin G