The covalent linking of two nucleotide analogues to antibodies

Two anticancer drugs, antagonists of nucleic acids, were covalently linked to antibodies specifically reactive with B leukemia cells and thus with a potential possibility of drug targeting to the tumor site. The drugs cytosine 1-beta-D-arabinoside and 5-fluorouridine, competitive inhibitors of enzymes involved in DNA synthesis, were linked to antibodies via a dextran bridge. Cytosine 1-beta-D-arabinoside was linked to periodate-oxidized dextran and fluorouridine to dextran hydrazide. The dextran derivatives were in turn linked to antibodies that recognized a specific membrane IgM on B leukemia cells. The drug-antibody conjugates maintained most of the original antigen-binding capacity of the antibody and the full pharmacological activity of the drugs.