A new ITN pilot study to look at oral tolerance is now open and has enrolled its first subjects. The pilot, led by Lloyd Mayer, MD (Mount Sinai) and called “Pilot study to determine the immunogenicity of Immucothel® and oral tolerance induction with Biosyn Native KLH in healthy subjects,” is a first step in investigating oral tolerance mechanisms and their role in autoimmunity.
Oral tolerance refers to a regulatory immune response that arises from ingesting antigens orally. If at a later time antigen-specific lymphocytes interact with the same antigen, the immune system reacts in a suppressive, rather than inflammatory, manner. This phenomenon has been observed in animals as well as humans, and is likely a mechanism that evolved to prevent hypersensitivity to food allergens or gut flora. Previous work by Dr. Mayer and colleagues demonstrated that patients with inflammatory bowel disease (IBD) showed defects in their ability to develop oral tolerance to neoantigen (a novel antigen not previously encountered by humans), and interestingly that this same defect was also seen in first-degree relatives of those patients without IBD. The investigators hypothesize that a breakdown in oral tolerance may contribute to the development of autoimmune disease, and that this breakdown may have genetic underpinnings.
As a first step in studying oral tolerance mechanisms, this pilot study will determine whether Immucothel®, a neoantigen product containing Keyhole Lymphocyte Antigen (KLH), 1) is sufficiently immunogenic to produce a measureable immune response in healthy volunteers, and 2) can induce oral tolerance in healthy volunteers.
If the product is successful at inducing oral tolerance in healthy volunteers, the investigators plan to conduct an oral tolerance induction study in patients with IBD, type 1 diabetes, multiple sclerosis and ankylosing spondylitis to further uncover the relationship between oral tolerance and autoimmunity.
For more about the pilot, see the summary on the ITN website and at ClinicalTrials.gov.