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. 2022 Nov 21;23(22):14466. doi: 10.3390/ijms232214466

Figure 4.

Figure 4

Schematic representation of mast cell-targeted biologics and drugs approved, under development, or potentially useful for asthma treatment. Several immunological stimuli (allergens, super allergens, bacterial, fungal, and viral products, smoke extracts) can damage bronchial epithelial cells to release alarmins, such as thymic stromal lymphopoietin (TSLP) [187,196], IL-33 [196,197], and IL-25 [196,198,199]. Monoclonal antibodies (mAbs) targeting TSLP (tezepelumab) [188,189], IL-33 (etokimab, itepekimab, tozorakimab) [200,201] (NCT04570657), or the IL-33 receptor ST2 (astegolimab) [202], have been approved or are under investigation for asthma treatment. mAbs targeting IL-5, produced by human mast cells [203], such as mepolizumab [204,205,206,207], reslizumab [208,209], or its receptor IL-5Rα (benralizumab) [175,210,211], have been approved for the treatment of eosinophilic asthma. Dupilumab blocks IL-4Rα and is approved for severe asthma [169,170,171]. Omalizumab was the first mAb approved for asthma treatment [212]. Novel mAbs anti-IgE (ligelizumab, UB-221, GI-301, UCB-8600) are under investigation for allergic disorder treatment [213] (NCT05298215; NTC04444466). Other strategies to treat mast cell-driven disease include inhibitors of spleen tyrosine kinase (SYK) (GSK2646264), Bruton’s tyrosine kinase (BTK) (acalabrutinib, fenebrutinib, ibrutinib, remibrutinib), and Janus kinase (JAK) inhibitors (GDC-0214) [214]. Another strategy to inhibit or deplete mast cells is the use of mAb targeting Siglec-8 (lirentelimab, also known as AK002) (NCT03379311; NCT03436797; NCT04322708) or Siglec-6 (OK006) [215].