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Immunologic responses of progressive multiple sclerosis patients treated with an anti-T-cell monoclonal antibody, anti-T12

Multiple Sclerosis Unit of the Center for Neurologic Diseases, Division of Neurology, the Brigham and Women's Hospital; the Division of Tumor Immunology, Dana Farber Cancer Institute; and the Harvard Medical School, Boston, MA.

Twelve patients with progressive MS were treated with a murine IgM pan-T-cell monoclonal antibody reactive against T12, a determinant present on most post-thymic T-cells. Circulating T12 + cells could not be detected from days 1 to 7, although T3 + Til + T12 - cells appeared by day 3. Human anti-mouse antibodies were detected in 78% of patients by day 7 and correlated with a decrease in anti-T12 M Ab blood levels and the reappearance of T12 + cells in the blood. Although there were high levels of anti-T12 MAb in the serum, there were only barely detectable levels in the CSF and no decrease in the proportion of T12+ cells in the CSF with treatment. Immunologic studies demonstrated a decrease of in vitro pokeweed mitogen-driven Ig synthesis on day 3 with an increase on day 10 that consisted in part of human anti-mouse antibodies. Eleven of 12 patients completed therapy. Prednisone was administered with the treatment after mild allergic reactions occurred in the first two patients. Because this was an open phase one study and patients were treated with prednisone, the effect of treatment on the progression of disease is difficult to assess, and no definitive conclusions concerning clinical effects can be made.

Address correspondence and reprint requests to Dr. Hafler, Center for Neurologic Diseases, BSRB-12, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.

Supported by NIH grants NS17182, AI19801, and AI21226; by a grant from the National Multiple Sclerosis Society; and by the Albert J. and Diane E. Kaneb Charitable Lead Trust.

Dr. Hafler is the recipient of NIH Clinical Investigator Development Award NS00981 and is a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society.

Accepted for publication October 30, 1985.

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