**3. Other B cell targeting monoclonal antibodies**

#### **3.1 Anti-CD22 antibody epratuzumab**

Epratuzumab (Immunomedics, Inc.) is a humanized monoclonal IgG antibody that specifically targets the CD22 antigen on B cells (Leonard & Goldenberg 2007). This monoclonal antibody is 90% to 95% of human origin thus greatly reducing the potential for immunogenicity. Unconjugated anti-CD22 antibodies only partially deplete B cells, but might deliver a negative signal by binding CD22 to the cell surface (Daridon, Blassfeld et al. 2010). Treatment of SLE patients with epratuzumab leads to a reduction of circulating CD27 negative B-cells, although epratuzumab is weakly cytotoxic to B-cells *in vitro*. Epratuzumab binding was higher on B-cells relative to T-cells. In addition, weak non-specific binding of epratuzumab on monocytes was noted. On B-cells, binding of epratuzumab was enhanced on CD27negative B-cells compared to CD27 positive B-cells, primarily related to a higher expression of CD22 on CD27negative B-cells. Epratuzumab also enhanced the migration of CD27negative B-cells towards the chemokine CXCL12.

Recently, Dorner et al. reported the results of an open-label, single-center study of 14 patients with moderately active SLE (Dörner, Kaufmann et al. 2006). Patients received 360 mg/m2 of epratuzumab intravenously every 2 weeks for 4 doses with analgesic antihistamine premedication prior to each dose. Total BILAG scores decreased by 50% in all 14 patients at some point during the study with 92% having decrease in various amounts continuing to at least 18 weeks.

Epratuzumab toxicity consisted primarily of mild to moderate transient infusion–related events during the first infusion. These results support conducting multicenter controlled studies to examine the effects of epratuzumab in broader patient populations. A U.S. patent has been issued to Immunomedics, Inc. for epratuzumab as a potential new treatment for lupus.
