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Phase 1 clinical trial of chimeric monoclonal anti-CD4 antibody in multiple sclerosis
J W Lindsey1, S Hodgkinson, R Mehta
1Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA.
Insights
Chimeric anti-CD4 antibody cM-T412 effectively depletes CD4 lymphocytes in multiple sclerosis (MS) patients. This treatment was well-tolerated and showed potential for MS management.
Area of Science:
- Immunology
- Neurology
- Pharmacology
Background:
- Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
- CD4 lymphocytes play a critical role in the immune response and are implicated in MS pathogenesis.
- Targeting CD4+ T-cells is a potential therapeutic strategy for MS.
Purpose of the Study:
- To evaluate the safety and efficacy of cM-T412, a chimeric monoclonal anti-CD4 antibody, in patients with MS.
- To assess the impact of cM-T412 on CD4 lymphocyte counts and other immune cells.
- To monitor clinical and MRI outcomes in MS patients treated with cM-T412.
Main Methods:
- An open-label trial was conducted involving 29 patients diagnosed with MS.
- Patients received treatment with the chimeric monoclonal anti-CD4 antibody, cM-T412.
- CD4 lymphocyte counts were measured at baseline, 3 hours, 1 month, and 6 months post-treatment.
Main Results:
- cM-T412 induced rapid and sustained depletion of circulating CD4 (helper/inducer) lymphocytes.
- Mean CD4 counts decreased significantly post-treatment, with partial recovery by 6 months.
- Transient changes in other immune cells were observed, but no significant long-term effects.
- Common side effects included headache, nausea, myalgia, fever, and tachycardia, primarily in the early post-treatment period.
- No serious infections or unexpected adverse events were reported.
- Kurtzke EDSS scores remained stable, and MRI scans showed reduced contrast enhancement.
Conclusions:
- Treatment with cM-T412 is well-tolerated in MS patients at the tested doses.
- The antibody achieves long-lasting and selective depletion of CD4 lymphocytes.
- cM-T412 demonstrates potential as a therapeutic agent for managing MS.
Abstract:
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 long-lasting depletion of circulating CD4 (helper/inducer) lymphocytes. The mean (+/- SE) CD4 count for the group decreased from 870 (+/- 66) cells/mm3 at baseline to 76 (+/- 11) 3 hours after treatment, and then increased to 425 (+/- 38) at 1 month after treatment and 475 (+/- 39) at 6 months after treatment. Numbers of CD8 (cytotoxic/suppressor) lymphocytes, B lymphocytes, granulocytes, and monocytes changed transiently but showed no significant long-term effects. The most common side effects were headache, nausea, myalgia, fever, and tachycardia occurring in the first few hours after treatment. No serious or unexpected infections or other significant adverse effects occurred. Kurtzke EDSS scores remained stable, and MRI scans showed less contrast enhancement 1 week 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.