Work

Development and Characterization of 4A7: A High-Affinity Monoclonal Antibody Targeting Claudin18.2

Year: 2025

Type: article

Abstract: Purpose: Claudin18.2 has emerged as a promising therapeutic target due to its high expression in gastric (GC) and pancreatic cancers (PC). However, patients with advanced, unresectable, or metastatic GC or PC face poor prognoses, highlighting the urgent need for more effective Claudin18.2-targeted therapies. Methods and Results: We developed 4A7, a fully human monoclonal antibody with superior affinity and specificity for Claudin18.2, using a rigorous positive and negative screening strategy to eliminate cross-reactivity with Claudin18.1. In vitro, 4A7 demonstrated significantly enhanced binding activity, as well as robust antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), outperforming IMAB362, a clinical investigational antibody. In vivo, 4A7 exhibited remarkable tumor growth inhibition both as a monotherapy and in combination with anti-mPD-1, achieving superior efficacy compared to IMAB362. Additionally, 4A7 demonstrated a higher degree of humanization and comparable stability, supporting its translational potential. Conclusion: 4A7 shows great promise as a next-generation therapeutic for Claudin18.2-positive cancers, offering improved efficacy and reduced immunogenicity. This study not only highlights 4A7's potential to address unmet clinical needs but also provides a foundation for future innovations in monoclonal antibody-based cancer therapy.

Source: ImmunoTargets and Therapy

DOI: 10.2147/itt.s494696

Authors: Yahui Wu, Juan Tian, Yangyihua Zhou, Ran Zhang, Xiang Gao, Longlong Luo

Institution: Hunan Normal University

Language: English

Topic: Monoclonal and Polyclonal Antibodies Research

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,320