Skin Immunoengineering to Induce Long-Lasting Systemic Immune Tolerance to Food Allergens
Abstract
Food allergy (FA) is a highly prevalent, potentially life-threatening health condition that poses a tremendous burden on affected people, their families, health care providers, and the medical system. Despite the significant challenges associated with FA, there is still no effective therapy for FA, with durable clinical benefits, and the standard of care for FA remains strict avoidance of food allergens and uninterrupted access to epinephrine auto-injectors at the risk of severe adverse effects, including anaphylaxis. These mainstays of FA management are unsatisfactory for affected people, and thus, FA patients are prone to high morbidity rates, and the emergency room visits associated with FA have significantly increased over the past decade. Further, constant vigilance due to strict dietary restrictions causes a high level of stress and anxiety for affected individuals and for their families, leading to poor quality of their lives. Due to the lack of effective therapies for FA, there are other critical impacts of FA beyond affected individuals and their families: (1) FA places pressure on local neighborhoods and schools, industry practices, and government policy; and (2) FA has national security implications because a diagnosis of FA renders people ineligible to join the military, posing challenges to recruit and maintain the operationally ready Service Members. As such, the increasing prevalence of FA over the past decade and the lack of safe and effective therapies for FA highlight the ongoing considerable challenges associated with the management of FA. The aforementioned challenges associated with FA translate into a pressing need for the development of safe, well-tolerated, inexpensive, highly effective, and broadly applicable therapies for FA. Over the past decade, there has been increasing research dedicated to the investigation of food allergen-specific immunotherapy (ASIT) as a disease-modifying strategy that has the potential to lead to desensitization and protection against accidental food allergen exposure. Despite great advances in the development of ASIT for FA, the existing ASIT methods result in low and transient efficacy, bear the risk of severe adverse effects, including anaphylactic reaction, because of systemic allergen exposure, and suffer from poor patient adherence and high cost due to a large number of clinical visits over several years. The goal of our project is to develop an entirely novel immunoengineering strategy for FA to obviate the shortcomings of existing ASIT methods, thereby leading to a safer, more effective, lower-cost, and more convenient ASIT for FA. Specifically, we propose to leverage our experience in skin immunobiology, biomaterials science, controlled release drug delivery, and immunology to devise a cutaneous immunoengineering platform based on microneedle patches (MnPs) that will exploit the emerging immune communication between the skin and other tissues (e.g., gastrointestinal tract) to induce long-term systemic tolerance to food allergens. As such, this project will directly address the Peer Reviewed Medical Research Program (PRMRP) Fiscal Year 2022 (FY22) Portfolio Strategic Goal of developing and testing a new treatment strategy to mitigate the inflammatory and/or allergic disease state under the PRMRP Topic Area of Food Allergies for the FY22 Portfolio of autoimmune disorders and immunology. The hypothesis of this proposal is that skin immunoengineering using multicomponent MnPs incorporating food allergens, tolerogenic immunomodulators, and lymph node-targeting nanoparticles (NPs) will generate long-lived allergen-specific systemic tolerogenic immune responses that will reverse the clinical symptoms of FA. Our strategy will rationally modulate the cutaneous immune system (1) at the time of food allergen delivery (in the immunoresponsive skin layers) and (2) at the time of allergen presentation to lymphocytes (in the skin-draining lymph nodes) to exploit the remarkab
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310168
Entities
People
- Emrullah Korkmaz
Organizations
- United States Army