Antibody-directed therapies for hematological malignancies

Malignant hematopoietic cells express lineage-restricted antigens that serve as suitable targets for antibody-directed therapy. Although several highly specific, potent and relatively nontoxic, engineered antibodies, immunoglobulin fragments and antibody conjugates have been developed, only three have gained approval for clinical use. Of these, a chimeric mouse–human anti-CD20 antibody has yielded the most impressive clinical results. Encouraging data with the other approved antibodies, and with agents in clinical trials, suggest that rational antibody design will generate effective products for several different hematological malignancies. Despite these advances, significant challenges remain in the identification of optimal cellular targets, antibody forms and treatment schedules for therapeutic applications. Antibody-based approaches have so far given rise to three approved agents that are safe and effective as monotherapy but may ultimately prove to be most useful as part of combined treatment regimens.