The anti‐mitozantrone monoclonal antibody NO‐1, protects acute leukaemia cell lines from the cytotoxic effects of mitozantrone

Abstract

The monoclonal antibody NO-1 was raised against the potent anti-cancer drug mitozantrone by immunization of a BALB/c mouse with a mitozantrone-keyhole limpet haemocyanin conjugate in Freund's complete adjuvant. This antibody was shown to be highly effective in vitro at neutralizing the cytotoxic effects of mitozantrone for the acute leukaemia cell lines ALL-1 and MOLT4. In order to achieve complete protection, a drug to antibody molar ratio of 1.5:1 was required. The neutralizing effect was specific for mitozantrone, as NO-1 antibody offered no protection of the MOLT4 cell line to the cytotoxic effects of the anthracycline drug daunorubicin when used at a near identical molar ratio. NO-1 antibody has already proven a highly successful monoclonal reagent for use in a competitive enzyme-linked immunosorbent assay for the accurate and sensitive quantitation of mitozantrone in serum. The neutralizing properties of NO-1 suggest other possible applications for this antibody. These could include a use in the rapid clearance of pharmacologically active mitozantrone from the circulation following very high dose administration prior to bone marrow transplantation and for the construction of bispecific antibodies for targeting mitozantrone to tumour cell populations.