PRT120 Mechanism of Action

 

Principle: The acquisition of tolerance is achieved through immunomodulation of the body’s response to the allergen. Prota’s proprietary oral immunotherapy has been shown to have immunomodulatory effects that are expected to support acquisition of oral tolerance.

 

PRT120 REDIRECTS THE IMMUNE RESPONSE FROM ALLERGY towards TOLERANCE

Mechanism: In allergic individuals, an inappropriate T helper 2 (Th2) response has developed to the food allergen(s) leading to production of peanut-specific IgE antibodies (sIgE) and differentiation of mast cells. Upon re-exposure to peanut, peanut allergens bind to peanut sIgE antibodies on the surface of the mast cells, and crosslinking of adjacent peanut sIgE antibodies results in activation of mast cells, triggering the release of mast cell mediators which in turn lead to the symptoms of an allergic reaction.

The immune modulating actions of PRT120 direct the immune system to respond differently to peanut allergen, supporting a tolerance-type response in place of an allergic response. Over time there is redirection of the peanut-specific immune response away from allergy towards tolerance. Prota’s clinical studies have shown that children who achieve sustained unresponsiveness / remission after treatment have significant reduction in blood levels of peanut sIgE as well as Ara h 2 sIgE, indicating redirection of the underlying peanut allergy. Importantly, these reductions in blood levels of peanut and Ara h 2 sIgE antibodies are long-lasting, with greater than 85% reduction in levels persisting to 12-months post-treatment3.

Approach:

Prota Therapeutics is developing an innovative novel treatment for peanut allergy, based on over a decade of research by the company’s scientific founder, Prof Mimi Tang.

In a randomized controlled clinical study, administration of PRT120 has been shown to:

  • reduce peanut skin prick test wheal size,
  • reduce peanut specific IgE levels in the blood,
  • increase peanut specific IgG4 levels in the blood

These changes were maintained at 12-months after treatment was withdrawn3.

Further investigation of the mode of action of PRT120 is underway.

 

References:

  1. W. Burks, H. A. Sampson, M. Plaut, G. Lack and C. A. Akdis. Treatment for food allergy. J Allergy Clin Immunol 2018 Vol. 141 Issue 1 Pages 1-9. Accession Number: 29307409 DOI: 10.1016/j.jaci.2017.11.004
  2. S.E. Ashley, A. C. Jones, D. Anderson, P. G. Holt, A. Bosco and M. L. K. Tang. Remission of peanut allergy is associated with rewiring of allergen-driven T helper 2-related gene networks. Allergy 2022 Vol. 77 Issue 10 Pages 3015-3027. Accession Number: 35615783 PMCID: PMC9790273 DOI: 10.1111/all.15324
  3. Loke, F. Orsini, A. C. Lozinsky, M. Gold, M. D. O’Sullivan, P. Quinn, et al. Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial. Lancet Child Adolesc Health 2022 Vol. 6 Issue 3 Pages 171-184. Accession Number: 35123664 DOI: 10.1016/S2352-4642(22)00006-2
  4. Loke, X. Wang, M. Lloyd, S. E. Ashley, A. C. Lozinsky, M. Gold, et al. Allergy 2024. Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study. Accession Number: 39099231 DOI: 10.1111/all.16262