Mechanism of action and resistance to monoclonal antibody therapy

Monoclonal antibodies (MoAbs) are increasingly used in the treatment of patients with hematological malignancies and autoimmune diseases. The most commonly employed humanized and chimeric MoAbs are rituximab, alemtuzumab (Campath-1H, Ilex Pharmaceuticals, San Antonio, TX), and gemtuzumab-ozogamicin (Mylotarg, Wyeth-Ayerst Laboratories, St Davids, PA). The mechanism of action of these antibodies, and host and cellular factors influencing the response, are not completely known. Induction of apoptosis, antibody-dependent cell cytotoxicity (ADCC), and complement-mediated cell death (CDC) is the proposed mechanism of action of these antibodies. We review the current understanding of the mechanism of action of and resistance to these MoAbs.