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Review
. 2018 Sep;193(3):275-283.
doi: 10.1111/cei.13159.

Immunotherapy with oral administration of humanized anti-CD3 monoclonal antibody: a novel gut-immune system-based therapy for metaflammation and NASH

Y Ilan  1 , K Shailubhai  2 , A Sanyal  3
Affiliations
Review

Immunotherapy with oral administration of humanized anti-CD3 monoclonal antibody: a novel gut-immune system-based therapy for metaflammation and NASH

Y Ilan et al. Clin Exp Immunol. 2018 Sep.

Abstract

The immune system plays a role in the pathogenesis of non-alcoholic steatohepatitis (NASH) underlying hepatocyte injury and fibrosis progression at all disease stages. Oral administration of anti-CD3 monoclonal antibody (mAb) has been shown in preclinical studies to be an effective method for systemic immune modulation and alleviates immune-mediated disorders without T cell depletion. In the present review, we summarize the concept of the oral administration of humanized anti-CD3 mAb in patients with NASH and discuss the potential of this treatment to address the current requirements of treatments for NASH. Recently published preclinical and clinical data on oral administration of anti CD3 are discussed. Human trials have shown that the oral administration of anti-CD3 in healthy volunteers, patients with chronic hepatitis C virus (HCV) infection and patients with NASH and type 2 diabetes is safe and well tolerated, as well as biologically active. Oral anti-CD3 induces regulatory T cells, suppresses the chronic inflammatory state associated with NASH and exerts a beneficial effect on clinically relevant parameters. Foralumab is a fully human anti-CD3 mAb that has recently been shown to exert a potent anti-inflammatory effect in humanized mice. It is being developed for treatment of NASH and primary biliary cholangitis (PBC). Oral administration of anti CD3 may provide an effective therapy for patients with NASH.

Keywords: NAFLD; NASH; anti CD3; oral tolerance; treatment.

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Figures

Figure 1
Figure 1
Schematic presentation of the mechanism of action of foralumab in non‐alcoholic steatohepatitis (NASH). After the oral administration of anti‐CD3 monoclonal antibody (mAb), the antibody is established in the small bowel and mesenteric lymph nodes. Foralumab, a specific anti‐CD3 epsilon mAb, binds T lymphocytes in the gut and modulates the CD3/T cell receptor (TCR complex), thus eliminating T cell proliferation and the release of proinflammatory cytokines. Binding leads to tolerogenic cross‐talk between dendritic cells and lymphocytes in the gut‐associated lymphoid tissue and mesenteric lymph nodes, thus promoting systemic regulatory T cells and the secretion of anti‐inflammatory cytokines which alleviate the chronic inflammatory state in target organs in NASH.
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References

    1. Wong VW, Chitturi S, Wong GL et al. Pathogenesis and novel treatment options for non‐alcoholic steatohepatitis. Lancet Gastroenterol Hepatol 2016; 1:56–67. - PubMed
    1. da Cunha AP, Weiner HL. Induction of immunological tolerance by oral anti‐CD3. Clin Dev Immunol 2012; 2012:425021. - PMC - PubMed
    1. Musso G, Cassader M, Gambino R. Non‐alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies. Nat Rev Drug Discov 2016; 15:249–74. - PubMed
    1. Perazzo H, Dufour JF. The therapeutic landscape of non‐alcoholic steatohepatitis. Liver Int 2017; 37:634–47. - PubMed
    1. Rotman Y, Sanyal AJ. Current and upcoming pharmacotherapy for non‐alcoholic fatty liver disease. Gut 2017; 66:180–90. - PubMed

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