UCLA researchers in the David Geffen School of Medicine and CNSI have developed a nanoparticle that induces antigen tolerance for use in treatment of allergy and autoimmune diseases.
BACKGROUND:
When the body’s immune overreacts against environmental allergens or falsely recognizes the body’s own molecular components as foreign, the results can be serious systemic allergic disorders or autoimmune diseases. Antigen-specific immune tolerance is a desired goal for treatment of allergic and autoimmune diseases, whereby the immune system is ‘trained’ to actively turn off the immune response to the allergens or autoimmune antigens. More specifically, immune, tolerogenic therapies can be implemented to train a subset of immune cells, known as the regulatory T-cells to suppress the immune response to allergens and autoimmune antigens. One pathway by which this can be accomplished is to rely on the antigen presenting cells of the liver, which specializes in tolerogenic immune responses . Nanoparticle-based therapies provide a powerful means of inducing this tolerance, by being designed to encapsulate the antigens and display the surface targeting sequence that sends them to the liver. The liver can then generate regulatory T-cells that can go to any organ in the body that participates in analytical autoimmune reactions. These targeted nanoparticle therapies, provide the means to inducing highly specified immune tolerance, as opposed to widespread immunosuppression that is currently induced to treat allergy and autoimmune disorders in the clinic. These less specific immunomodulating treatments frequently lead to adverse treatment effects, , including suppression of the immune response to pathogens. Therefore, in order to avoid the usage of immunomodulators with widespread deleterious effects on the patient, there is a need to advance on available antigen-specific tolerizing therapeutics.
INNOVATION:
Antigen specific interventions for allergies and autoimmune disorders—two groups of disorders characterized by patients’ hyperactive immune response against non-pathogenic bodies—are limited in number and efficacy; however, UCLA researchers present a novel nanoparticle based therapeutic platform that induces immune tolerance towards a predetermined antigen in animal models. Through targeting of tolerogenic antigen presenting cells in the liver, researchers demonstrated, as a proof of principle, that administration of nanoparticles to mouse models of asthma and anaphylaxis can reduce these potentially fatal systemic allergic disorders. There is also preliminary evidence that the same is true in animal models for rheumatoid arthritis, lupus, and type I diabetes. Importantly, the tolerogenic effect can be obtained by using intact, antigens or representative epitopes in these disease models, thereby avoiding the need for nonspecific immunosuppression or immune modulatory therapies. The tolerogenic nanoparticle platform is earmarked for treatment of a wide range of allergic disorders and autoimmune diseases.
POTENTIAL APPLICATIONS:
• Autoimmune disease treatment.
• Allergy desensitization and treatment.
• Prevention of Allergic reactions to Therapeutic proteins and Medications
ADVANTAGES:
• Treats cause rather than symptoms for allergies/autoimmune diseases
• Targets a novel cell type in the liver that exert widespread control over systemic immune responses.
• Can be designed for intact allergens as well as specific epitopes.
• Can treat a wide variety of diseases characterized by overactive, misguided immunity.
DEVELOPMENT-TO-DATE:
Researchers have demonstrated efficacy of inducing tolerance for a protein target in animal models of asthma and anaphylaxis.
Related Papers (from the inventors only)
Liu Q, Wang X, Liu X, Kumar S, Gochman G, Ji Y, Liao YP, Chang CH, Situ W, Lu J, Jiang J, Mei KC, Meng H, Xia T, Nel AE. Use of Polymeric Nanoparticle Platform Targeting the Liver To Induce Treg-Mediated Antigen-Specific Immune Tolerance in a Pulmonary Allergen Sensitization Model. ACS Nano. 2019, 13, 4778-4794.