Oral anti-CD3 antibodies for SLE

Wu, H. et al. Suppression of murine SLE by oral anti-CD3: inducible CD4+CD25−LAP+ regulatory T cells control the expansion of IL-17+ follicular helper T cells. Lupus 18, 586–596 (2009).

Defects in the number and function of regulatory T (T_REG) cells are thought to have a key role in the pathogenesis of systemic lupus erythematosus (SLE). Research by Howard Weiner and colleagues shows that oral administration of anti-CD3 antibodies to lupus-prone SNF1 mice results in the development of an inducible subset of CD4⁺CD25⁻LAP⁺ T_REG cells, and blocks disease development and progression in this animal model.

Mice that received anti-CD3 antibodies developed less-severe glomerulonephritis and produced lower levels of pathogenic autoantibodies targeting double-stranded DNA (dsDNA) than control mice. In addition, this treatment led to increased numbers of suppressive CD4⁺CD25⁻LAP⁺ T_REG cells, which produced more transforming growth factor β than comparable cells from control mice. Reduced numbers of inflammatory IL-17⁺CD4⁺ICOS⁺CXCR5⁺ follicular helper T cells, CD138⁺ plasma cells and CD73⁺ mature memory B cells were detected in anti-CD3-treated mice in comparison with control mice. In animals with established disease, anti-CD3 treatment reduced the levels of anti-dsDNA autoantibodies and improved survival.

“Clinically applicable strategies to generate inducible T_REG cells in vivo could have beneficial effects in the treatment of SLE,” explains Henry Yim Wu, the corresponding author. “Our positive results in animals with ongoing disease raise the possibility that oral anti-CD3 antibodies might be an effective immunomodulatory therapy for SLE that could be easily and rapidly applied to human subjects.”