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 : 2025-06-01 Epub 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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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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基于曲妥珠单抗框架，通过人工智能驱动的噬菌体展示筛选发现her2特异性抗体的新策略

人表皮生长因子受体2 （HER2）是一个公认的药物靶点，是各种癌症治疗的关键靶点，需要发现更多的抗体用于治疗和检测目的。在这里，我们通过人工智能驱动的噬菌体显示筛选（AIPDS）开发了一种创新的抗体生成工作流程。该工作流程集成了人工智能驱动的抗体CDRH3序列设计、高通量DNA合成和噬菌体展示筛选。我们应用AIPDS工作流程生成了针对人表皮生长因子受体2 （HER2）的有希望的抗体，为流线型抗体生成提供了模板。7种新型抗体脱颖而出，在各种功能分析中显示出有希望的功效。值得注意的是，DYHER2-02在所有实验测试中表现出强大的性能。总之，我们的研究引入了一种新的方法，使用人工智能辅助噬菌体展示方法来产生现有抗体的新抗体变体。这些新的抗体变体在研究、诊断和治疗方面具有潜在的应用。

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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.