A newly introduced liver-targeted allergen immunotherapy (LIT) tested in mice shows promise in providing rapid, safe and long-term control of allergic asthma. This new approach is addressed in the study, “Liver-Targeted Allergen Immunotherapy Rapidly and Safely Induces Antigen-Specific Tolerance to Treat Allergic Airway Disease in Mice,” and was published in the journal, Science Translational Medicine.
The research addresses the limitations of current asthma treatments, which primarily manage disease symptoms but fail to address the underlying cause of allergic disease. According to the study’s authors, allergen immunotherapy holds the promise for durable disease control by establishing allergen-specific tolerance through repeated introduction of native allergens. However, its efficacy can be limited by long interventions, reactions upon administration and poor patient compliance.
Researchers from the Pritzker School of Molecular Engineering at the University of Chicago developed LIT tolerogens from native respiratory allergens, which induced antigen-specific regulatory T (Treg) cells in vivo with only two interventions. Synthetic mannosylation of native allergens prevented antibody-mediated recognition and subsequent life-threatening anaphylaxis upon administration. Protein engineering prevented sensitization events that occurred because of the proteolytic activity of native respiratory allergens, which limit the effectiveness of allergen immunotherapy.
Upon completion of the study, researchers announced the following highlights:
- Rapid and safe treatment: The LIT method involves only two interventions, significantly reducing the duration and frequency of treatment compared to traditional allergen immunotherapy.
- Efficacy in preclinical models: In mouse models of allergic asthma, LIT effectively reduced clinical, pathological and serological symptoms. The treatment’s success was dependent on the induction of antigen-specific regulatory T (Treg) cells.
- Long-term control: Sensitized mice treated with LIT experienced yearlong control of allergic asthma symptoms without additional interventions.
- Promising therapy: The approach showed encouraging results against Der p 1, a major protein in house dust mite (HDM) allergens, providing symptom relief in mice with established HDM allergy.
According to the study’s authors, the research data provides a proof of concept that LIT with synthetically mannosylated tolerogens provides a rapid, safe and effective approach to allergen immunotherapy and holds promise for future clinical applications that can provide a significant, durable improvement in the quality of life for asthma patients.
