As a consequence of the invention of the hybridoma technology by K�hler and Milstein (1 ), many monoclonal antibodies (MAbs) have been evaluated in clinical trials since the early 1980s. Clinical outcomes were generally poor (2 –5 ), with the notable exception of marked tumor responses, including long-term remissions of patients with malignant B-cell lymphoma who were treated with patient-specific antiidiotypic antibodies (6 –8 ). The main factors responsible for these initial shortcomings were related to the immunogenicity of the murine protein, to modulation of targeted antigens, and to the poor ability of these antibodies to sufficiently mediate antibody-dependent effector functions in humans.
