Remission Induction in Patients with Lymphoid Malignancies Using Unconjugated CAMPATH-1 Monoclonal Antibodies.

Abstract

CAMPATH-1 (CDw52) antigen is a heavily glycosylated, non-modulating glycoprotein expressed abundantly on the cell surface of nearly all normal and malignant lymphocytes but not on hemopoietic stem cells. A series of rat monoclonal antibodies (MAbs) with CDw52 specificity but of varying immunoglobulin isotype has been produced, and assessed for ability to deplete lymphoid cells in patients with lymphoproliferative disorders. Although all IgM, IgG2a and IgG2b rat MAbs were able to elicit lysis with human complement in vitro, only the IgG2b MAb (CAMPATH-1G) could elicit substantial lymphoid depletion in vivo. The efficacy of CAMPATH-1 G probably results from its ability to bind human Fc receptors and activate cell-mediated lysis of antibody-coated cells. Twenty-nine patients with lymphoid malignancies have received between 250 mg and 680 mg of CAMPATH-1G; nine of these attained complete remission A human MAb with CDw52 specificity has been produced by "grafting" the complementarity-determining regions (CDRs) of the rat MAb into human IgG1 heavy- and kappa light-chain genes. These constructs were transfected into a rat myeloma cell line. Sufficient human MAb (CAMPATH-1H) has been purified to treat two patients with non-Hodgkin's lymphoma in leukemic phase. Although each patient only received approximately 100 mg of MAb, remission was induced in both patients with recovery of normal hemopoiesis during the course of therapy CDw52 MAbs are the first MAbs to demonstrate consistent anti-tumor effects in vivo and may have roles in the therapy of a wide range of lymphoid malignancies and as powerful immunosuppressive agents.