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菌体的生产和功能分析显示了针对EGFR/HER2二分化域的scFv重组抗体

Mina Dabiri¹, Mohsen Tehrani², Alireza Rafiei²

¹Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Center (MCBRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Biomedical and Biological Sciences, Rowan University, 201 Mullica Hill Rd, Glassboro, NJ, 08028, United States.

Protein expression and purification

|December 26, 2024

概括

一种针对表皮生长因子受体 (EGFR) 分解域的新型单链可变片段 (scFv) 抗体有效抑制了EGFR和HER2的分解. 这种scFv对EGFR过度表达瘤的向治疗具有前途.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
免疫治疗是一种免疫疗法.

背景情况:

瘤细胞通过利用表皮生长因子受体 (EGFR) 家族来对Herceptin等疗法产生耐药性.
在表达这些受体的癌症中,EGFR和HER2二分化是导致治疗失败的关键机制.
针对EGFR-HER2相互作用对于克服治疗耐药性至关重要.

研究的目的:

开发和评估人类复合单链可变片段 (scFv) 抗体.
抑制EGFR的二分化域,特别是阻止其与HER2的相互作用.
评估这种scFv作为EGFR过度表达癌症的向治疗的潜力.

主要方法:

反EGFR scFv抗体的表达和净化.
使用细胞ELISA,MTT测定,STAT3酸化抑制和定量RT-PCR进行功能性表征.
对scFv结构和EGFR结合亲和力的计算研究.
对EGFR-HER2二聚化抑制的评估.

主要成果:

净化后的scFv显示与EGFR结合,通过细胞ELISA和免疫血清测试得到证实.
在表达EGFR/HER2的癌细胞系中,scFvs显著降低了扩散和存活率 (MCF7,MDA-MB-468,SKOV3).
经过治疗的MCF7细胞显示STAT3酸化降低,Bcl-2减少,Bax表达增加,这表明诱导了亡.
该scFv成功地阻碍了EGFR和HER2的二分化.

结论:

开发出来的scFv抗体有效地阻断了EGFR和HER2的二分化.
这种功能性阻塞表明scFv作为向治疗剂的潜力.
scFv是治疗各种EGFR过度表达瘤的有希望的候选人.

关键词:

模度化域是一个模度化域.欧洲农业基金会 (EGFR) 是一个基金.对于ErbB受体来说,这是一个很好的选择.在HER2中,HER2是HER2.scFvv 在线阅读

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