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Oral tolerance: can we make it work?

Yaron Ilan1

  • 1Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel. ilan@hadassah.org.il

Human Immunology
|June 30, 2009
PubMed
Summary
This summary is machine-generated.

Mucosal tolerance offers a promising, low-toxicity treatment for immune-mediated diseases. Overcoming challenges in human trials requires optimizing delivery, antigen presentation, and patient selection for successful clinical application.

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Area of Science:

  • Immunology
  • Gastroenterology
  • Autoimmune Diseases

Background:

  • Mucosal tolerance is a promising strategy for treating autoimmune and inflammatory diseases due to its low toxicity and ability to promote antigen-specific immune responses.
  • Despite observed benefits in animal models, clinical trials have shown limited success over the past two decades, raising concerns about human applicability.

Purpose of the Study:

  • To address key questions hindering the successful clinical application of oral tolerance for immune-mediated disorders in humans.
  • To identify critical factors for translating animal model successes into effective human therapies.

Main Methods:

  • Discussion of 12 major questions concerning oral tolerance and its clinical use.
  • Review of strategies for targeting gut-liver axis cells, improving antigen presentation, and optimizing dose and formulation.
  • Consideration of mucosal adjuvants, immune biomarkers, combination therapies, and patient population selection.

Main Results:

  • Limited success in human clinical trials suggests a gap between animal models and human application.
  • Successful human application hinges on multifaceted strategies addressing cellular targeting, antigen presentation, formulation, adjuvants, biomarkers, and patient selection.

Conclusions:

  • Translating oral tolerance to human therapies requires addressing specific challenges in the gut-liver axis and immune response modulation.
  • Future success depends on a comprehensive approach involving targeted strategies and careful patient selection for immune-mediated diseases.