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The Covalent Binding of Daunomycin and Adriamycin to Antibodies, with Retention of Both Drug and Antibody Activities

Departments of Chemical Immunology [E. H., R. L., R. M., R. A., M. S.] and Biophysics [M. W.] The Weizmann Institute of Science, Rehovot, Israel

Daunomycin and adriamycin, two potent cancer chemotherapeutic agents, were linked to immunoglobulins, making use of various covalent cross-linking methods. The most suitable method for binding of the drugs to the antibodies, which retained both antibody and drug activity, was periodate oxidation of the drug, followed by the linking of the oxidized drug to the immunoglobulin and subsequent reduction of the product with sodium borohydride. The activity of the drug-antibody conjugates was tested in vitro on tumor and normal cell cultures and was found to be similar to that of the free drug. A significant amount of antibody activity was retained, as found both with anti-bovine serum albumin antibodies, assayed by chemically modified bacteriophage, and with anti-mouse tumor antibodies, assayed by C'-dependent cytotoxicity.

¹ Fellow of the Helen Hay Whitney Foundation. Permanent address: Department of Medical Oncology, Stanford Medical School, Stanford, Calif.

Received 11/ 4/74. Accepted 1/20/75.

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