Signaling antibodies in cancer therapy

Over the past 10-15 years, genetic engineering of monoclonal antibodies has greatly improved their utility in humans and in particular their ability t o recruit immunological effecters such as natural killer cells and macropha ges. Clinical results now confirm that these new reagents, when directed at the appropriate tumor markers (e.g. CD20 or Her-2), can control disease wi thout untoward side effects. However, despite such success it is still uncl ear exactly how monoclonal antibodies (mAbs) destroy tumors in vivo. She ab ility of mAbs to crosslink membrane receptors and generate intracellular si gnals is part of the mechanism by which they control tumor growth. New data show that such 'signaling' mAbs can be used to sensitize tumors to the act ion of conventional DNA-damaging drugs.