Certain features that make an antigen a good candidate for antibody therapy have 
been defined. CD52 is a 21- to 28-kd nonmodulating cell surface 
glycosylphosphatidylinositol-linked glycoprotein that is abundantly expressed 
(up to 5 x 10(5) molecules per cell) on most normal and malignant lymphocytes 
and monocytes. Its functions are unknown. CD52 is an excellent target for 
complement-mediated lysis and antibody-dependent cellular cytotoxicity. A series 
of rat and genetically reshaped human CD52 antibodies has been assessed for the 
ability to deplete lymphocytes in vivo to induce immunosuppression and for the 
treatment of lymphoid malignancies. CD52 antibodies that activate both 
complement and antibody-dependent cellular cytotoxicity consistently deplete 
lymphocytes from blood, spleen, and bone marrow but are less effective against 
lymph node disease or extranodal masses. CD52 antibodies provide effective 
therapy for chronic leukemias, such as T-cell prolymphocytic leukemia and some 
subtypes of B-cell chronic lymphocytic leukemia, that may be resistant to 
conventional chemotherapy. For example, most patients with T-cell prolymphocytic 
leukemia, including those with large tumor burdens and high peripheral white 
blood cell counts, will enter complete remission using the antibody CAMPATH-1H 
without any evidence of tumor lysis. In contrast, in chronic lymphocytic 
leukemia, CD52 antibodies may be more effective in the setting of minimal 
residual disease and may allow harvesting of uncontaminated stem cells. Further 
experiments to enhance the activity of CD52 antibodies in sites refractory to 
antibody alone are currently being undertaken.