2. Academic Validation
  3. Development of a novel humanized anti-TSLP monoclonal antibody HZ-1127 with anti-allergic diseases and cancer potential

Development of a novel humanized anti-TSLP monoclonal antibody HZ-1127 with anti-allergic diseases and cancer potential

  • Antib Ther. 2024 Feb 27;7(2):123-130. doi: 10.1093/abt/tbae006.
Xiaolei Liu 1,  Jianzhong Han 2,  Qian Wang 3,  Peng Wang 2,  Li Li 3,  Kehe Du 3,  Fengchao Jiang 3,  Pei Zhang 3,  Hongjun Liu 3,  Jian Huang 2 4 5
Affiliations

Affiliations

  • 1 Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3500 N Broad St, Philadelphia, PA 19140, USA.
  • 2 Department of Research, Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ 08103, USA.
  • 3 Department of Research, IPHASE Therapeutic Ltd., 422 Industrial Dr. North Wales, PA 19454, USA.
  • 4 Department of Center for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, 3500 N Broad St, Philadelphia, PA 19140, USA.
  • 5 Department of Biomedical Sciences, Cooper Medical School of Rowan University, 303 Cooper St, Camden, NJ 08102, USA.
PMID: 38566968 DOI: 10.1093/abt/tbae006
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.

Keywords

HZ-1127; Humanized; anti-TSLP; development; monoclonal antibody; novel.

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