Normally, epithelial cells immediately produce “alarmin” cytokines when stimulated by potentially threatening external environments, such as allergens, bacteria, viruses, and worms. These alarmins then alert the immune system to these threats, thereby mobilizing host immune defense mechanisms.

IL-33 is a member of the IL-1 family and also is an alarmin. It can bind with heterodimeric receptors which are composed of IL-1 receptor accessory protein and the transmembrane isoform of ST-2. Once IL33 binds to its receptor ST2, the cytoplasmic domain of ST2 recruits the adaptor protein MyD88. And then ignites NF-κB and AP-1 signaling pathways and induces the expression of proinflammatory molecules. Some researches suggest that targeting the alarmins has good immunomodulatory effects. Today, we will introduce a trial drug targeting the IL-33/ST-2 pathway — Itepekimab.

Itepekimab (REGN-3500) is a mAb of IL-33 for Inflammation Research

 Itepekimab (REGN-3500) is a monoclonal antibody of IL-33. Firstly, Itepekimab can reduce the number of eosinophils in the blood of ex-smokers. Secondly, Itepekimab can reduce airway inflammation and related tissue damage in previous clinical studies. Meanwhile, Itepekimab has clinical activity in asthma. Furthermore, Itepekimab has a potential role in chronic obstructive pulmonary disease (COPD) and pediatric atopic dermatitis (AD).

To sum up, Itepekimab (REGN-3500) is a mAb of IL-33 and can be used for the research of inflammation.

Reference:

[1] Wechsler ME, et al. N Engl J Med. 2021 Oct 28;385(18):1656-1668.

[2] Rabe KF, et al. Lancet Respir Med. 2021 Nov;9(11):1288-1298.

[3] Jongho Ham, et al. Immune Netw. 2022 Feb;22(1):e11