George J. Schreiber and David E. Kerr* Pages 616 - 629 ( 14 )
Monoclonal antibodies (mAb) that bind to tumor-associated antigens have been used to selectively deliver toxic agents such as drugs, radionuclides, or protein toxins to tumors. A number of mAb conjugates have been effective in killing tumor cells in vitro and in causing tumor regressions in mice; but as yet have not been curative against solid tumors in humans. One of the problems that has been identified for mAb tumor targeting is that systemic clearance tends to be slow, resulting in low tumor-to-blood ratios even many days after administration. Many strategies have been explored to accelerate mAb conjugate clearance without affecting intratumoral uptake. This can be accomplished by extracorporeal adsorption or plasmapheresis to remove the conjugate from the blood, or by complexing the conjugate with an agent that is cleared very quickly from the blood. Such agents include carbohydrates, avidin, and mAbs directed against the immunoconjugate. Each of these strategies have been employed to enhance the tumor-to- blood ratio of immunoconjugates.