Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
The Effects of the Anti-CD22 Monoclonal Antibody Epratuzumab on Peripheral Blood B Cells and Immune Responses In Vivo, and Immunoglobulin Production In Vitro.
Shock1, Anthony, Brown2, Derek, Crook2, Kenneth, Shaw2, Stevan, Bourne2, Timothy, Foulkes2, Roland, Rose2, Geoffrey
Epratuzumab is a humanized monoclonal antibody against CD22 currently being evaluated clinically in patients with systemic lupus erythematosus (SLE). The aim of the current study in cynomolgus monkeys was to investigate the effects of epratuzumab on circulating B cell numbers and on the immune response to the challenge antigens keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT). Additionally, the effect of epratuzumab on immunoglobulin production from human B cells in culture was assessed.
In one study, cynomolgus monkeys received 4 weekly doses of epratuzumab at 10, 60, or 160 mg/kg and peri-pheral blood CD20+ B cell numbers were enumerated by flow cytometry. In a second study, cynomolgus monkeys received epratuzumab at 3 different dose levels (1 × 60 mg/kg, 1 × 10 mg/kg or 4 × 60 mg/kg), or saline. The primary immune response to administered KLH and the secondary immune response to TT were then monitored over time using ELISAs to measure anti-TT and anti-KLH titers in serum. Human peri-pheral blood mono-nuclear cells (PBMC) or purified B cells from human tonsils were cultured in vitro with a range of stimuli and the effect of epratuzumab on IgG and IgM production, assessed by ELISA, was monitored after 5 days in culture.
There was a 5060% reduction in the numbers of circulating B cells in cynomolgus monkeys after treatment with epratuzumab at all doses tested, which occurred within 24 hours of dosing. Animals treated with saline showed a primary anti-KLH response, with an increase in both IgG and IgM antibody levels. Epratuzumab did not inhibit this response at any dose tested, and there was no significant difference between the groups when area under the curve of the response over time for each animal was assessed. A robust IgG anti-TT was demonstrated but, again, no significant difference was observed between the differently dosed groups and saline controls. The production of IgG and IgM from human PBMC or tonsil B cells in culture was unaffected by incubation with a range of concentrations of epratuzumab.
Epratuzumab treatment caused a reduction in B cells but had no effect on the capacity to raise an antibody response to challenge antigens in cynomolgus monkeys in vivo. The production of immunoglobulin by B cells in culture was also unaffected by epratuzumab. This might indicate that the efficacy of epratuzumab in SLE patients is unlikely to be accompanied by a gross effect on the capacity to generate an adaptive immune response.
To cite this abstract, please use the following information:
Shock, Anthony, Brown, Derek, Crook, Kenneth, Shaw, Stevan, Bourne, Timothy, Foulkes, Roland, et al; The Effects of the Anti-CD22 Monoclonal Antibody Epratuzumab on Peripheral Blood B Cells and Immune Responses In Vivo, and Immunoglobulin Production In Vitro. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :752