| Autor: |
Konner J. Jackson, Cassandra Buhl, Shannon M. Miller, Juhienah K. Khalaf, Janine Ward, Cherrokee Sands, Lois Walsh, Margaret Whitacre, David J. Burkhart, Hélène G. Bazin-Lee, Jay T. Evans |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology, Vol 15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2024.1421758 |
| Popis: |
IntroductionAtopic diseases have been steadily increasing over the past decades and effective disease-modifying treatment options are urgently needed. These studies introduce a novel synthetic Toll-like receptor 4 (TLR4) agonist, INI-2004, with remarkable efficacy as a therapeutic intranasal treatment for seasonal allergic rhinitis.MethodsUsing a murine airway allergic sensitization model, the impact of INI-2004 on allergic responses was assessed.ResultsOne or two intranasal doses of INI-2004 significantly reduced airway resistance, eosinophil influx, and Th2 cytokine production – providing strong evidence of allergic desensitization. Further investigations revealed that a liposomal formulation of INI-2004 exhibited better safety and efficacy profiles compared to aqueous formulations. Importantly, the liposomal formulation demonstrated a 1000-fold increase in the maximum tolerated intravenous dose in pigs. Pre-clinical GLP toxicology studies in rats and pigs confirmed the safety of liposomal INI-2004, supporting its selection for human clinical trials.DiscussionThese findings lay the groundwork for the ongoing clinical evaluation of INI-2004 in allergic rhinitis as a stand-alone therapy for individuals poly-sensitized to multiple seasonal allergens. The study underscores the significance of innovative immunotherapy approaches in reshaping the landscape of allergic rhinitis management. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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