Extreme reactions to food results in over 30,000 incidents of anaphylaxis and between 100 - 200 deaths in the US each year. Allergies to tree nuts (TN), such as almond, cashew, hazelnut and walnut, are collectively the second most common triggers of anaphylaxis behind peanut. An estimated million Americans are allergic to TNs with many impacted by exposure to trace amounts and no recourse but to stringently avoid ingestion or risk a potentially fatal anaphylactic episode. In response to NIAID's commitment to address the health challenge posed by food allergies, , Immunomic Therapeutics, Inc. ("ITI") proposes innovative SBIR Phase I research to design a novel multivalent TN immunotherapy that utilizes a lysosomal associated membrane protein ("LAMP") chimeric construct to direct the major TN allergens of almond, hazelnut, cashew, and walnut into the MHC II / endosomal pathway. ITI envisions a novel therapeutic product consisting of 4 plasmids, each encoding the major TN allergens as a LAMP chimera. When administered, this product, TN-LAMP-vax, is expected to rapidly desensitize subjects to the encoded allergens and cross reactive allergens by inducing a helper T-cell type 1 (Th1) response. The proposed therapeutic product is anticipated to be a safe, hypoallergenic, and cost-effective immunotherapy that significantly reduces or eliminates sensitivity to TN allergens. ITI has successfully designed, tested and validated multiple antigen-LAMP-vax DNA formulations, including multivalent peanut and cedar allergy vaccines. Recently, ITI completed a Phase I clinical study of JRC-LAMP-vax, an immunotherapeutic for treating Japanese red cedar allergy through administration of the major cedar allergen Cry j 2. When administered intramuscularly as naked DNA in saline four times, biweekly, no severe adverse events were reported and skin test conversion from Japanese red cedar positive to negative was observed in 14 out of 16 patients at the end of the trial at day 132. The putative mechanism of action behind this result is suggested by previous work with LAMP that shows immunization initiates a Th 1 response, high titers of immunoglobulin (Ig) G, and immunological memory. The Th1 and IgG immune response provides a compelling argument in support of LAMP vaccines to treat IgE-mediated allergic diseases. The LAMP vaccine immune response follows the accepted medical paradigm for allergy de-sensitization and establishes a new level of safety by eliminating exposure to free allergen as required in traditional immunotherapy. This Phase I research draws on ITI's experience in commercializing LAMP-based allergy vaccines and completion of the Aims will clearly provide a rationale for commercializing the therapeutic TN vaccine for allergic patients. Phase I Aims are to: (1) design and synthesize TN allergen-encoding plasmids;(2) evaluate and optimize immunogenicity of TN-LAMP-vax;and (3) evaluate TN-LAMP-vax in single TN and multi-nut anaphylaxis animal model and optimize dosing and delivery. During Phase II, ITI will prepare TN-LAMP-vax, under current Good Manufacturing Practices (cGMP) and conduct biodistribution &toxicology studies in support of an IND filing. The goal of this project is to commercialize TN-LAMP-vax. ITI strongly believes that this proposal supports NIAID's commitment to address the health challenge posed by food allergy and TN-induced anaphylaxis, for which there is no treatment.
TNs are a common cause of food allergies in the US. TN allergies have become more prevalent over the last decade and now affect 1% of Americans. TN allergies are rarely overgrown. An immunotherapy that desensitizes TN allergies would greatly impact patients with food allergy by helping to prevent potentially fatal anaphylactic reactions and providing a significant improvement in quality of life.