Antibody-dependent drug therapy

Many drugs, especially quinidine and heparin, induce antibodies leading to thrombocytopenia. In most cases the antibodies are drug-dependent however, there are many examples in which the antibodies are autoimmune in nature [42], even for drugs, such as quinidine that are classically associated with drug-dependent antibodies [43], Gold therapy, in particular, is associated with autoimmune-thrombocytopenia [44],... 

Another innovation based on a similar concept is to link the pretargeted antibody to an inactive cytotoxic drug that is later switched on by injecting an enzyme (45). This has been called antibody-dependent enzyme prodrug therapy (ADEPT), and may be an advance on simply attaching cytotoxics to antibodies, in which case their efficacy is reduced and toxicity increased (46). 

Ultimately, the cost of immunosorbent isolation will depend on the entire process and must be evaluated against alternative processes. Consider, as an example, the costs and decisions involved in the purification of urokinase. One course of drug therapy consists of 33 mg of urokinase (4,000,000 CTA units). At the hospital pharmacy the drug costs for one course of treatment are currently 3,000 (9), or 91,000/gram. There are approximately 76,000 patients in the U.S. that could be treated with urokinase therapy each year requiring an annual production of approximately 2,500 g. We have selected a monoclonal antibody that has allowed the purification of urokinase from urine, tissue culture media, and bacterial culture media in a single step with 85% retention of urokinase activity (6). This monoclonal antibody was immobilized at 2 gL l with an immobilization yield of 0.8 and a cycle half number of 300 cycles. The urokinase capacity for the first cycle would be 1.2 gL l of immunosorbent. 

Immune thrombocytopenia during rifampicin therapy has been attributed to drug-dependent binding of an IgG antibody to platelets the binding epitope of the antibody was found in the glycoprotein Ib/IX complex (38). 

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