New research into allergic diseases is ongoing, especially the development and application of new biological agents. A researcher at the American College of Allergy, Asthma and Immunology (ACAAI), mentioned that traditional asthma treatments are ineffective for some people whose asthma cannot be controlled. Biologics are at the forefront of treatment because of their potential to personalize therapy to treat the cells that cause allergic inflammation and make breathing difficult for some people. To date, many biologics targeting Th2/1/17 inflammatory biomarkers are available, many of which are already in clinical use.
Fig.1 Application of biologics in allergic diseases.1
Biologics Targeting IgE
IgE plays a central role in the development of allergic diseases. Targeting IgE molecules is one of the most important ways to eliminate allergic reactions in the body and produce lasting effects. Omalizumab is a recombinant humanized IgG1 monoclonal antibody for asthma. It specifically binds to the upper FcεR site of free IgE in the blood circulation, thereby blocking the binding of lgE to target cells such as mast cells and basophils, reducing the release of inflammatory mediators and thereby improving the inflammatory response, and can be used in the treatment of allergic asthma, chronic urticaria.
Biologics Targeting Interleukin
In eosinophilic allergic asthma, naive T cells differentiate and mature into Th2 cells, Th2 cells promote the release of immunoglobulins and cytokines, including interleukin (IL)-3, IL-4, IL-5 and IL-13, and stimulates B lymphocytes to produce IgE. Therefore, the development idea of a class of biologics is to develop antibodies against these interleukins. For example, blocking the IL-5 receptor with mepolizumab did reduce severe eosinophilic asthma and severe uncontrolled asthma. A biologic agent inhibits the IL-4/IL-13 axis by targeting the IL-4Rα subunit for the treatment of chronic sinusitis caused by eczema, asthma, and nasal polyps. Nemolizumab, targeting IL-31 receptor A (IL-31RA), alleviates pruritic symptoms and IL-31 signaling in the pathogenesis of atopic dermatitis (AD).
Biologics Targeted Signaling Pathways
Some biologics target signaling pathways. For example, targeting the JAK/STAT signaling pathway is critical for T cell activation and can also block downstream pathways of many important cytokine receptors. T cells play an important role in allergic inflammation. Therefore, JAK/STAT pathway inhibition represents an effective and feasible therapeutic approach for AD. In addition, asthma is often accompanied by inflammation, and many proinflammatory chemokines, cytokines, adhesion molecules, etc. are upregulated through the NF-κB transcription factor family. Thus, asthma and NF-κB-mediated signaling are inextricably linked. Some biologics can alleviate certain asthma symptoms and accelerate recovery by targeting these signaling pathways, which has important reference significance for designing and choosing the best drug regimen.
Currently, identifying new and reliable biomarkers and elucidating novel molecular mechanisms that persist in specific responses have become important research directions. For example, chemotactic receptor homologous molecule (CRTH2) expressed on TH2 cells is involved in inducing the migration and activation of Th2 lymphocytes, eosinophils and basophils. Currently, some CRTH2 antagonists such as AMG853 and BI671800 have been developed for the treatment of allergic diseases such as asthma. In addition, other treatments for allergies are also being continuously improved and optimized, such as traditional pharmacological treatments for allergic diseases and allergen immunotherapy, which are still used in the mainstream. Experienced scientists at Creative Biolabs have built a professional non-IgG antibody research platform to provide non-IgG therapeutic antibodies services for allergic diseases therapy. If you are interested, please contact us for more information.
Reference
- Wang, J., et al. “Pathogenesis of allergic diseases and implications for therapeutic interventions.” Signal Transduction and Targeted Therapy 8.1 (2023): 138.
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