A new strategy to HER2-specific antibody discovery through artificial intelligence-powered phage display screening based on the Trastuzumab framework

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-07 DOI:10.1016/j.bbadis.2025.167772

Mancang Zhang , Qiangzhen Yang , Jiangrong Lou , Yang Hu , Yongyong Shi

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引用次数: 0

Abstract

Human epidermal growth factor receptor 2 (HER2) is a recognized drug target, and it serves as a critical target for various cancer treatments, necessitating the discovery of more antibodies for therapeutic and detection purposes. Here, we have developed an innovative workflow for antibody generation through Artificial Intelligence-powered Phage Display Screening (AIPDS). This workflow integrates artificial intelligence-driven antibody CDRH3 sequence design, high-throughput DNA synthesis and phage display screening. We applied AIPDS workflow to generate promising antibodies against the human epidermal growth factor receptor 2 (HER2), offering a template for streamlined antibody generation. Seven novel antibodies stood out, demonstrating promising efficacy in various functional assays. Notably, DYHER2–02 demonstrates strong performance across all experimental tests. In summary, our study introduces a novel methodology to generate new antibody variants of an existing antibody using an AI-assisted phage display approach. These new antibody variants hold potential applications in research, diagnosis, and therapeutic applications.

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.