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If unmodified monoclonal antibodies are to be used for effective therapy, careful attention must be paid to isotype and specificity. The optimum istoypes of rodent and human antibodies for interaction with human effector mechanisms have been defined using matched sets of antibodies. Some antigens are much better targets than others and the CAMPATH-1 antigen (CDw52) is a particularly good example. A rat IgG2b CAMPATH-1 antibody proved to be rather effective for depleting human lymphocytes in vivo but therapy could be limited by anti-globulin responses. A reshaped human antibody with the same specificity was constructed by genetic engineering. This has been used in the treatment of two patients with lymphoma with the clearance of large numbers of tumour cells from blood, marrow, spleen and lymph nodes. We believe that this antibody will be a potent immunosuppressant as well as being useful as a component of therapy for lymphoid malignancies.
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