The role of alemtuzumab in the treatment of chronic lymphocytic leukemia.

摘要

Alemtuzumab, a rat derived humanized IgG1kappa monoclonal antibody, targets the orphan membrane molecule CD52, which has no known physiological function . CD52 has a restricted expression which includes lymphocytes, monocyte/macrophages, eosinophils, and only a minority of granulocytes and CD34~+ precursor hematopoietic cells . CD52 is expressed at high levels in CLL, but has variable expression in other types of malignant lymphocytes . In CLL, alemtuzumab is highly effective against malignant B cells in the blood, less effective in the bone marrow and least effective in bulky lymph nodes and the spleen. Possible explanations for this selective effect include limited tissue penetration by the large antibody molecules, less complement and fewer effector cells in the nodes and spleen, and the protective properties of stromal microenvironments. The mechanism of action of alemtuzumab in CLL is poorly understood. Although alemtuzumab is very effective at causing complement dependent cytotoxicity, the role of antibody dependent cytotoxicity is less well defined and there is no proven role for direct induction of apoptosis . However, because cytotoxicity is apoptosis independent, alemtuzumab is highly effective against CLL cells with 17p13-that are usually resistant to purine analogues. Alemtuzumab thus represents a novel and potentially very useful drug in the management of patients with CLL.