EXPRESSION AND CHARACTERIZATION OF CM-T413, A CHIMERIC ANTI-CD4 ANTIBODY WITH IN-VITRO IMMUNOSUPPRESSIVE ACTIVITY

Anti-CD4 monoclonal antibodies (mAbs) have shown considerable promise in the treatment of rheumatoid arthritis, psoriasis, and allograft rej ection and may have potential use in blocking HIV-1 infection. One suc h anti-CD4 mAb we have developed, chimeric M-T412 (or cM-T412), has be en used in clinical trials to treat rheumatoid arthritis, generalized postular psoriasis, and other autoimmune diseases. Here we report the cloning and expression of a second chimeric anti-CD4 mAb using M-T413, a murine mAb that blocks HIV-1 infection of H9 cells. We cloned the i mmunoglobulin light and heavy chain variable regions of M-T413, combin ed them with the human kappa (light chain) or G1, G2, G3, and G4 (heav y chain) constant regions in human expression vectors, and expressed t hese chimeric mAbs in 653 cells. Like chimeric M-T412 IgG1, the chimer ic M-T413 mAbs inhibit T-cell proliferation in the mixed lymphocyte re sponse and thus can act to immunosuppress CD4(+) T-cell response. In c ontrast to M-T412, however, the M-T413 chimeric mAbs have reduced acti vity in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay using human CD4(+) target and effector cells. We conclude that the chi meric M-T413 mAbs have potential utility in treating autoimmune diseas e and may be useful as prophylactics in preventing HIV-1 infection.