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Targeting Leukocyte Trafficking in Inflammatory Bowel Disease

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Abstract

In the last two decades, understanding of inflammatory bowel disease (IBD) immunopathogenesis has expanded considerably. Histopathological examination of the intestinal mucosa in IBD demonstrates the presence of a chronic inflammatory cell infiltrate. Research has focused on identifying mechanisms of immune cell trafficking to the gastrointestinal tract that may represent effective gut-selective targets for IBD therapy whilst avoiding systemic immunosuppression that may be associated with off-target adverse effects such as infection and malignancy. Integrins are cell surface receptors that can bind to cellular adhesion molecules to mediate both leukocyte homing and retention. In 2014, Vedolizumab (Entyvio®) was the first anti-integrin (anti-α4ß7 monoclonal antibody) treatment to be approved for use in IBD. Several other anti-integrin therapies are currently in advanced stages of development, including novel orally administered small-molecule drugs. Drugs targeting alternative trafficking mechanisms such as mucosal addressin cellular adhesion molecule-1 and sphingosine-1-phosphate receptors are also being evaluated. Here, we summarise key established and emerging therapies targeting leukocyte trafficking that may play an important role in realising the goal of stratified precision medicine in IBD care.

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Authors and Affiliations

  1. Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK

    Nicola J. Wyatt, R. Alexander Speight, Christopher J. Stewart, John A. Kirby & Christopher A. Lamb

  2. Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK

    Nicola J. Wyatt, R. Alexander Speight & Christopher A. Lamb

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  1. Nicola J. Wyatt
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  2. R. Alexander Speight
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  3. Christopher J. Stewart
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  4. John A. Kirby
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  5. Christopher A. Lamb
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Correspondence to Christopher A. Lamb.

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No sources of funding were used to conduct this study or prepare this manuscript.

Conflicts of interest

Dr R Alexander Speight has received grants from Genentech and personal fees from Dr Falk Pharma, Janssen, AbbVie, Tillotts and Takeda, outside the submitted work. Dr Nicola Wyatt, Dr Christopher Stewart, and Prof. John Kirby have no conflicts of interest that are directly relevant to the content of this article. Dr Christopher Lamb has received grants from Genentech, AbbVie, Eli Lilly, Pfizer, Roche, UCB Biopharma, Sanofi Aventis, Biogen IDEC, Orion OYJ and AstraZeneca; personal fees from Dr Falk Pharma and Ferring; and grants and personal fees from Janssen and Takeda, all outside the submitted work.

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NJW and CAL planned the manuscript content, which was drafted by NJW. CAL provided critical review during manuscript drafting and supervised the work. All other authors (RAS, CJS, and JAK) critically reviewed the manuscript. All authors approved the final manuscript.

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Wyatt, N.J., Speight, R.A., Stewart, C.J. et al. Targeting Leukocyte Trafficking in Inflammatory Bowel Disease. BioDrugs 35, 473–503 (2021). https://doi.org/10.1007/s40259-021-00496-5

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