[Preparation of a monoclonal antibody (HI30)-mitomycin C conjugate utilizing dextran T-40 and its specific cytotoxicity against human leukemia cell line CEM].
The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified murine monoclonal antibody (HI30) to a human T lymphocyte surface differentiation antigen with dextran T-40 as the intermediate carrier. The conjugate (HI30:MMC molar ratio, 1:7) retained full antibody binding activity as determined by an indirect immunofluorescence assay. E. Coli HB101 growth inhibition test showed that the antimicrobial activity [MMC equivalent (microgram/ml)] of the conjugate was about 29.2% as potent as free MMC. In a cytotoxicity test, the conjugate was about 3-10 times more cytotoxic against the antibody-reactive human T lymphocyte leukemia CEM cells than was free MMC or the mixture of HI30 and MMC [IC50 of the MMC equivalent (microgram/ml) was 0.4147, 2.212, 2.171, respectively] and was less cytotoxic against the antibody-nonreactive L1210 cells (IC50 were 1.311, 0.8683, 0.7308, respectively). The selective cytotoxicity was also confirmed by competitive inhibition with free antibody, showing a dependence on antibody binding of the target cell surface antigen. There was no detectable free MMC released from HI30-Dex-MMC conjugate stored at 4 degrees C for over one month as measured by chromatography on a Sephadex G-25 column.
Institute of Hematology, Tianjin.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D003911:Dextrans / Q000494:pharmacology; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000473:pathology*; D015458:Leukemia, T-Cell / Q000473:pathology*; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003911:Dextrans; D000922:Immunotoxins; D008937:Mitomycins; D016685:Mitomycin