Anti-CD52 antibody, alemtuzumab, binds to Langerhans cells in Langerhans cell histiocytosis

BACKGROUND: The humanized anti-CD52 monoclonal antibody, alemtuzumab (or Campath-1H), has been shown to potently deplete lymphocytes in human patients. It has been used to successfully treat graft versus host disease and chronic lymphocytic leukemia (CLL). CD52 is expressed on normal lymphocytes, monocytes, and some dendritic cell subsets. However, normal Langerhans cells (LC's) in the skin do not bind alemtuzumab. We sought to determine whether the pathologic LC's of Langerhans cell histiocytosis (LCH) express CD52 and thus could be targeted by this antibody. METHODS: Immunohistochemistry was performed on both frozen and fixed/paraffin-embedded tissue specimens using either Campath-1G (the parental rat isotype) or Campath-1H (the humanized version of Campath in clinical use). RESULTS: Both Campath-1H and Campath-1G were found to bind to the pathologic LC's in LCH, but not the normal LC's of skin. Specific staining was demonstrated in all (13 of 13) LCH specimens examined, though staining was somewhat variable among specimens, and tended to be weaker in paraffin-embedded specimens. CONCLUSIONS: Expression of CD52 by the pathologic LC's seen in LCH suggests that alemtuzumab may represent a new, targeted therapy for this disease. Such therapy is particularly needed for patients with refractory, high-risk disease. Further investigation of the possible clinical use of this antibody in these patients is warranted.