PHASE-1 CLINICAL-TRIAL OF CHIMERIC MONOCLONAL ANTI-CD4 ANTIBODY IN MULTIPLE-SCLEROSIS

We conducted an open trial of cM-T412, a chimeric monoclonal anti-CD4 antibody, in 29 patients with MS. This antibody caused a prompt and lo ng-lasting depletion of circulating CD4 (helper/inducer) lymphocytes. The mean (+/-SE) CD4 count for the group decreased from 870 (+/-66) ce lls/mm3 at baseline to 76 m(+/-11) 3 hours after treatment, and then i ncreased to 425 (+/-38) at 1 month after treatment and 475 (+/-39) at 6 months after treatment. Numbers of CD8 (cytotoxic/suppressor) lympho cytes, B lymphocytes, granulocytes, and monocytes changed transiently but showed no significant long-term effects. The most common side effe cts were headache, nausea, myalgia, fever, and tachycardia occurring i n the first few hours after treatment. No serious or unexpected infect ions or other significant adverse effects occurred. Kurtzke EDSS score s remained stable, and MRI scans showed less contrast enhancement 1 we ek after treatment. We conclude that treatment of MS patients with cM- T412 chimeric anti-CD4 antibody is well tolerated at the doses tested and produces a long-lasting, selective depletion of CD4 lymphocytes.