Liu Xiaolei, Han Jianzhong, Wang Qian, Wang Peng, Li Li, Du Kehe, Jiang Fengchao, Zhang Pei, Liu Hongjun, Huang Jian
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3500 N Broad St, Philadelphia, PA 19140, USA.
Department of Research, Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ 08103, USA.
Antib Ther. 2024 Feb 27;7(2):123-130. doi: 10.1093/abt/tbae006. eCollection 2024 Apr.
Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family and has been widely recognized as a master regulator of type 2 inflammatory responses at barrier surfaces. Recent studies found dysregulation of the TSLP-TSLP receptor (TSLPR) pathway is associated with the pathogenesis of not only allergic diseases but also a wide variety of cancers including both solid tumors and hematological tumors. Thus, the blockade of TSLP represents an attractive therapeutic strategy for allergic diseases and cancer. In this study, we report the development of a novel humanized anti-TSLP monoclonal antibody (mAb) HZ-1127. Binding affinity, specificity, and ability of HZ-1127 in inhibiting TSLP were tested. HZ-1127 selectively binds to the TSLP cytokine with high affinity and specificity. Furthermore, HZ-1127 dramatically inhibits TSLP-dependent STAT5 activation and is more potent than Tezepelumab, which is an FDA-approved humanized mAb against TSLP for severe asthma treatment in inhibiting TSLP-induced CCL17 and CCL22 chemokines secretion in human peripheral blood mononuclear cells. Our pre-clinical study demonstrates that HZ-1127 may serve as a potential therapeutic agent for allergic diseases and cancer.
胸腺基质淋巴细胞生成素（TSLP）是白细胞介素-2细胞因子家族的成员，已被广泛认为是屏障表面2型炎症反应的主要调节因子。最近的研究发现，TSLP-TSLP受体（TSLPR）途径的失调不仅与过敏性疾病的发病机制有关，还与包括实体瘤和血液肿瘤在内的多种癌症的发病机制有关。因此，阻断TSLP是一种针对过敏性疾病和癌症颇具吸引力的治疗策略。在本研究中，我们报告了一种新型人源化抗TSLP单克隆抗体（mAb）HZ-1127的研发情况。测试了HZ-1127的结合亲和力、特异性以及抑制TSLP的能力。HZ-1127以高亲和力和特异性选择性地结合TSLP细胞因子。此外，HZ-1127显著抑制TSLP依赖的STAT5激活，并且在抑制人外周血单核细胞中TSLP诱导的CCL17和CCL22趋化因子分泌方面比Tezepelumab更有效，Tezepelumab是一种经美国食品药品监督管理局批准用于治疗严重哮喘的抗TSLP人源化单克隆抗体。我们的临床前研究表明，HZ-1127可能是一种用于治疗过敏性疾病和癌症的潜在治疗药物。
