2. Academic Validation
  3. Development of a novel humanized anti-TSLP monoclonal antibody, QX008N, and exploration of combination therapy of anti-TSLP antibody and anti-IL-4R antibody

Development of a novel humanized anti-TSLP monoclonal antibody, QX008N, and exploration of combination therapy of anti-TSLP antibody and anti-IL-4R antibody

  • Int Immunopharmacol. 2024 Dec 5;142(Pt A):113102. doi: 10.1016/j.intimp.2024.113102.
Xiaomu Wang 1,  Yong Kong 2,  Tianquan Qiu 3,  Tao Chen 2,  Yuzhi Liu 2,  Gaoyong Shi 2,  Qiuping Sun 2,  Wei Chen 2,  Juan Zhang 4,  Jiwan Qiu 5
Affiliations

Affiliations

  • 1 Antibody Engineering Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
  • 2 Qyuns Therapeutics Co., Ltd., Taizhou, Jiangsu, China.
  • 3 WLSA Shanghai Academy, Shanghai, China.
  • 4 Antibody Engineering Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: zhangjuan@cpu.edu.cn.
  • 5 Qyuns Therapeutics Co., Ltd., Taizhou, Jiangsu, China. Electronic address: qiujiwan@qyuns.net.
PMID: 39276452 DOI: 10.1016/j.intimp.2024.113102
Abstract

Background: Severe asthma is a complex and chronic respiratory disease, and current conventional treatments are not effective in controlling the patients' condition. Thymic stromal lymphopoietin (TSLP) is a key regulatory factor in the initiation and maintenance of asthma. Thus, blocking TSLP during allergic inflammation emerges as a promising therapeutic approach; however, novel anti-TSLP therapies remain to be developed. Furthermore, the importance of Other signaling molecules, such as IL-4 and IL-13, should be considered. Moreover, to the best of our knowledge, the inhibitory effect of binding upstream and downstream signaling molecules has not been assessed.

Purpose: This study aimed to develop a novel, humanized anti-TSLP antibody and explore the enhancement in its efficacy when combined with anti-IL-4R antibodies to treat asthma.

Results: QX008N, derived from a rabbit antibody platform, exhibits a high affinity for TSLP and superior efficacy in blocking TSLP-induced signaling pathways and inflammation in vitro compared with Tezepelumab. In a cynomolgus monkey asthma model, QX008N ameliorated lung function and reduced the levels of eosinophils and IgE. Moreover, the coadministration of QX008N with anti-IL-4R antibodies enhanced the inhibition of inflammatory mediator production triggered via costimulation in vitro. In mouse asthma models, the simultaneous blockade of TSLP and IL-4R using anti-TL4R and anti-TSLP surrogates surpassed the efficacy of monotherapy. To the best of our knowledge, the therapeutic effect of a combination of anti-TSLP and IL-4R antibodies in an asthma model has not yet been reported.

Conclusion: These results furnish comprehensive preclinical evidence for QX008N as an innovative anti-TSLP therapeutic agent and provide a preliminary rationale for the development of combination therapies that simultaneously target the TSLP and IL-4R signaling pathways.

Keywords

Asthma; Combination therapy; Humanized TSLP monoclonal antibody; IL-4 receptor α; TSLP.

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