Bispecific Antibody Targeting Both IL33 and TSLP for Asthma and COPD

作者：Haitao Ran, Jianmin Huang, H. Li, L. Dong, David Liu, Ying Zhou, Chuan Su, Chao Chen, Ximing Xu, Xin Chen, Lü Tian, Jianjun Peng, Zhe Zhu · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2025 · DOI：10.1164/ajrccm.2025.211.abstracts.a1382 · 被引用次数：5 · 研究领域：Asthma and respiratory diseases

Abstract RATIONALE: Asthma and chronic obstructive pulmonary disease (COPD) are persistent inflammatory airway disorders characterized by obstructive airflow limitation, imposing a substantial burden on both patients and healthcare systems. Alarmins IL33 and TSLP have been established as validated therapeutic targets for the treatment of asthma and COPD. Notably, IL33 and TSLP are the only targets that have demonstrated clinical efficacy in non-Th2 asthma settings. Here we engineered and produced HXN-1013, a bispecific antibody (bsAb) simultaneously targeting both TSLP and IL33, with the aim to further enhance clinical efficacy for the treatment of asthma and COPD patients. METHODS: anti-TSLP antibodies were generated, characterized and selected through various in vitro assays, including TSLPR-STAT5-Luc reporter assays, TSLP-induced Baf3 proliferation, and CCL17 release from PBMCs. IL33 antibodies were generated and assessed using IL33 reporter assay, and L33 induced PBMC activation assay. The synergistic effect of dual targeting was measured by IL5 and IL13 release in human PBMCs co-stimulated with TSLP and IL33. RESULTS: Multiple anti-TSLP antibodies were generated with high potency and different binding epitopes, including antibodies targeting TSLP Site I (TSLPR binding site), Site II (IL7Rα binding site), and biparatopic antibodies that simultaneously targeting both site I and II. In TSLPR/STAT5 reporter assays and BaF3 proliferation assays, these antibodies demonstrated ...