开发具有抗过敏和抗癌潜力的新型人源化抗 TSLP 单克隆抗体 HZ-1127

Q2 Medicine Antibody Therapeutics Pub Date : 2024-02-27 DOI:10.1093/abt/tbae006
Xiaolei Liu, Jianzhong Han, Qian Wang, Peng Wang, Li Li, Kehe Du, Fengchao Jiang, Pei Zhang, Hongjun Liu, Jian Huang
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引用次数: 0

摘要

摘要 胸腺基质淋巴细胞生成素(TSLP)是IL-2细胞因子家族的成员,被广泛认为是屏障表面2型炎症反应的主调节因子。最近的研究发现,TSLP-TSLP 受体(TSLPR)通路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 是治疗过敏性疾病和癌症的一种有吸引力的策略。在这项研究中,我们报告了新型人源化抗 TSLP 单克隆抗体(mAb)HZ-1127 的开发情况。我们测试了 HZ-1127 的结合亲和力、特异性和抑制 TSLP 的能力。HZ-1127 可选择性地与 TSLP 细胞因子结合,具有很高的亲和力和特异性。此外,HZ-1127 还能显著抑制 TSLP 依赖的 STAT5 激活,在抑制 TSLP 诱导的 CCL17 和 CCL22 趋化因子在人外周血单核细胞中的分泌方面,HZ-1127 比 Tezepelumab(美国食品及药物管理局批准用于治疗严重哮喘的针对 TSLP 的人源化 mAb)更有效。我们的临床前研究表明,HZ-1127 可作为过敏性疾病和癌症的潜在治疗药物。
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Development of a novel humanized anti-TSLP monoclonal antibody HZ-1127 with anti-allergic diseases and cancer potential
Abstract 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.
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来源期刊
Antibody Therapeutics
Antibody Therapeutics Medicine-Immunology and Allergy
CiteScore
8.70
自引率
0.00%
发文量
30
审稿时长
8 weeks
期刊最新文献
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