Alemtuzumab and treatment of chronic lymphocytic leukemia and its immune-related disorders: One player on two tables

摘要

Alemtuzumab (Campath-1H; Genzyme, Cambridge, Mass., USA) is a chimeric recombinant IgG1 monoclonal antibody (hypervariable regions derived from rat IgG, responsible for antigen recognition and the human IgGl framework, to reduce immunogenicity) targeting the CD52 antigen [1]. Although its function is unknown, CD52 is present on normal and malignant human B and T lymphocytes, natural killer cells, monocytes and mac-rophages, but not on plasma cells or hematological precursors. The mechanisms of action of alemtuzumab have not been fully elucidated in detail. However, like ritux-imab, the binding of alemtuzumab to surface CD52 on target cells may cause cell death by three main mechanisms: complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and apoptosis. Unlike rituximab, alemtuzumab has also demonstrated the induction of in vitro cell death of chronic lymphocytic leukemia (CLL) cells through a mechanism that is independent of p53 status and caspase activation [2].