Immunomedics, Inc (MORRIS PLAINS, New Jersey), a biopharmaceutical company focusing on developing monoclonal antibodies to treat autoimmune diseases and cancer, reported results from a study showing epratuzumab, a humanized monoclonal antibody that targets the CD22 antigen found on peripheral blood B-cells, inhibits the increased activation and proliferation of B-cells in patients suffering from systemic lupus erythematosus (SLE) versus normal subjects.
CD22 is a B-cell-specific adhesion molecule and a coreceptor and negative regulator of the B-cell antigen receptor (BCR). In contrast to other anti-CD22 B-cell-depleting monoclonal antibodies such as rituximab (Rituxan; Genentech Inc; Mabthera; Roche Pharmaceuticals), epratuzumab acts as an immunomodulatory agent and does not drastically deplete circulating B-cells, but moderately reduces this population by 30% to 45%.
The current study is a follow-up to a phase I/II trial, in which epratuzumab was found to show indications of clinical activity and good safety in the treatment of patients with SLE. The first part of this study analyzed the effect of epratuzumab on peripheral blood B-cell subsets in 12 SLE patients. Results showed that the antibody preferentially targets naïve and transitional B-cells of these patients, which the company believes to be a unique difference compared with other anti-CD22 therapeutic monoclonal antibodies.
The second part of the study investigated the effect of epratuzumab on the inhibition of the activation of B-cells taken from a second group of 11 SLE patients and seven normal subjects. The enhanced B-cell activation and proliferation in SLE comprises T-cell-dependent and T-cell-independent pathways. Under in vitro experimental conditions designed to mimic polyclonal T-cell-independent B-cell activation (incubation with CpG) or T-cell-dependent costimulation (incubation with CD40L), epratuzumab preferentially blocked the enhanced activation and proliferation of anti-Ig-induced lupus B-cells versus normal B-cells.
Immunomedics has granted worldwide license of epratuzumab to UCB, SA, for the treatment of all autoimmune disease indications. UCB has development, manufacturing, and commercialization rights and is responsible for all clinical trials evaluating the antibody for the treatment of patients with moderate and severe lupus.
—A. Techman
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