We have produced an adriamycin-conjugated monoclonal antibody, AM1, covalently linked by acid-labile cis-aconitic spacer. The immunoconjugate, cisaconitic adriamycin (cAA)-AM1, was confirmed to retain the binding activity against human breast cancer cell lines by flow cytometry. The immunoconjugate was shown to be internalized into antigen-positive cancer cells by flow cytometry analysis and high performance liquid chromatography. Antitumor effects of cAA-AM1 were assessed on human breast cancer and colon cancer cell lines, with inhibition of 3H-leucine uptakes to the cells, c A A-AM1 demonstrated a selective cytotoxicity to ZR-75-1 which was reactive with AM1, whereas it showed no antitumor effect on SW1116 cells which did not react with AM1. Free adriamycin demonstrated a nonselective cytotoxicity against both cell lines. AM1 alone and cAA-control IgM did not show any antitumor effect on ZR-75-1. These results suggest that cAA-AM1 retains binding activity and specificity against breast cancer cells in vitro.
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