Basic and Clinical Studies of Transferrin-Adriamycin Conjugates: Mechanisms for a New Approach to Drug Targeting
Research in drug targeting to cancer cells is almost exclusively limited to monoclonal antibodies. The clinical use of monoclonal antibodies is frought with problems. Three of the most serious problems are antigen shedding, sensitization of the patient to mouse immunoglobulins, and mutation of the antigenic target. Antigen shedding is the antibody-induced disappearance of antigens from cell membranes. Drugs cannot exert cytotoxic effects if their antibody carriers are shed with antigen. The second problem is sensitization of patients to mouse immunoglobulins. Mouse proteins are antigenically foreign to the human immune system. Some patients mount hypersensitivity reactions to mouse immunoglobulins and are in danger of developing anaphylactic responses. The magnitude of this problem is shown by the finding that 50% of leukemia and lymphoma patients treated with monoclonal antibodies develop hypersensitivity reactions.1 The third problem with monoclonal antibodies relates to their restricted specificity. This is represented by cells that lose or mutate their surface antigens. Such cells are no longer recognized by cell-specific monoclonals and consequently acquire the ability to escape the anti-cancer effects of drugs conjugated to monoclonal antibodies.
KeywordsAcute Myelocytic Leukemia Transferrin Receptor Tritiated Thymidine Mouse Immunoglobulin Acute Myelogenous Leukemia Cell
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