Anti-TSLP antibodies: Targeting a master regulator of type 2 immune responses

• Nakajima Saeko

  Department of Dermatology, Kyoto University Graduate School of Medicine

• Kabata Hiroki

  Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine

• Kabashima Kenji

  Department of Dermatology, Kyoto University Graduate School of Medicine Singapore Immunology Network (SIgN), Skin Research Institute of Singapore (SRIS) and Agency for Science, Technology and Research (A^*STAR)

• Asano Koichiro

  Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine

抄録

TSLP is an epithelial cell-derived cytokine synthesized in response to various stimuli, including protease allergens and microorganisms like viruses and bacteria. Biological functions of TSLP require heterodimer formation between the TSLP receptor (TSLPR) and IL-7 receptor-α, which polarize dendritic cells to induce type 2 inflammation and directly expand and/or activate Th2 cells, group 2 innate lymphoid cells, basophils, and other immune cells. TSLP is thus considered a master regulator of type 2 immune responses at the barrier surfaces of skin and the respiratory/gastrointestinal tract. Indeed, genetic, experimental, and clinical evidence suggests that the TSLP-TSLPR pathway is associated with the pathogenesis of allergic diseases such as atopic dermatitis (AD) and asthma. Tezepelumab (AMG-157/MEDI9929) is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. A phase 2 trial for moderate to severe AD showed that a greater but not statistically significant percentage of tezepelumab-treated patients showed clinical improvements compared to the placebo group. A phase 2 trial for uncontrolled, severe asthma showed significant decreases in asthma exacerbation rate and improved pulmonary function and asthma control for tezepelumab-treated patients. Levels of biomarkers of type 2 inflammation, such as blood/sputum eosinophil counts and fraction of exhaled nitric oxide decreased, however, clinical efficacy was observed irrespective of the baseline levels of these biomarkers. A blockade of the TSLP-TSLPR pathway likely will exert significant clinical effects on AD, asthma, and other allergic diseases. The efficacy of anti-TSLP antibodies compared to other biologics needs to be further examined.

収録刊行物

• Allergology International

  Allergology International 69 (2), 197-203, 2020

  一般社団法人日本アレルギー学会

キーワード

• Asthma
• Atopic dermatitis (AD)
• Thymic stromal lymphopoietin (TSLP)
• Treatment
• TSLP receptor (TSLPR)

詳細情報

• CRID: 1390285300151582464
• NII論文ID: 130007833068
• DOI: 10.1016/j.alit.2020.01.001
• ISSN: 14401592
• ISSN: 13238930
• HANDLE: 2433/253927
• Web Site: https://api.elsevier.com/content/article/PII:S132389302030006X?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S132389302030006X?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2021023195
• 本文言語コード: en
• データソース種別:
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