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 rejection and may have potential use in blocking HIV-1 infection. One such anti-CD4 mAb we have developed, chimeric M-T412 (or cM-T412), has been 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 immunoglobulin light and heavy chain variable regions of M-T413, combined them with the human kappa (light chain) or G1, G2, G3 and G4 (heavy chain) constant regions in human expression vectors, and expressed these chimeric mAbs in 653 cells. Like chimeric M-T412 IgG1, the chimeric M-T413 mAbs inhibit T-cell proliferation in the mixed lymphocyte response and thus can act to immunosuppress CD4+ T-cell response. In contrast to M-T412, however, the M-T413 chimeric mAbs have reduced activity in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay using human CD4+ target and effector cells. We conclude that the chimeric M-T413 mAbs have potential utility in treating autoimmune disease and may be useful as prophylactics in preventing HIV-1 infection.
Looney
J E
JE
Department of Molecular Biology, Centocor, Inc., Malvern, Pennsylvania 19355.
Willinger
A
A
Lin
G
G
Rieber
E P
EP
Riethmuller
G
G
Ghrayeb
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D015342:DNA Probes; D004926:Escherichia coli; D005260:Female; D005818:Genetic Engineering; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000276:immunology*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins