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长循环的XTEN864-HGV-Apoptin融合蛋白用于选择性癌症治疗

Liu Yang¹, Akvile Haeckel¹, Nicola Beindorff²

¹Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiology, Charitéplatz 1, 10117 Berlin, Germany.

International journal of biological macromolecules

|March 4, 2025

概括

研究人员开发了一种基于Apoptin的新型融合蛋白,XTEN864-HGV-Apoptin,用于有效的静脉癌症治疗. 这种工程蛋白质在体内表现出强大的癌细胞杀死和延长血液循环.

科学领域:

生物化学生物化学
分子生物学分子生物学
在瘤学瘤学.

背景情况:

病毒蛋白CAV-Apoptin和HGV-Apoptin显示选择性杀死癌细胞,但不适合系统治疗.
需要开发基于阿波丁的融合蛋白来进行静脉输入的癌症治疗.

研究的目的:

为系统性癌症治疗设计和评估基于阿波丁的融合蛋白.
结合XTEN,MMP-2/9裂部位和TAT来提高输送和疗效.

主要方法:

在大肠杆菌中表达和净化XTEN864-HGV-Apoptin.
使用MTT和Annexin A5试验评估细胞毒性.
细胞吸收,血液半衰期,生物分布 (SPECT-CT) 和体内瘤生长抑制 (4T1模型) 的评估.

主要成果:

XTEN864-HGV-Apoptin已成功生产 (100 mg/L) 并进行净化.
融合蛋白显示出显著的癌细胞亡和减少生长,对正常细胞的毒性最小.
在体内研究表明,在小鼠中,血液循环延长 (17小时缓慢阶段) 和有效抑制瘤生长.

结论:

XTEN864-HGV-Apoptin表现出强大的癌症特异性细胞毒性和有利的药理学特性.
融合蛋白是开发系统适用,可生物降解和可产生大肠杆菌的抗瘤药物的有希望的候选者.

关键词:

乳腺癌乳腺癌乳腺癌肝细胞癌是肝细胞癌.长时间的血液循环.可以通过MMP激活的聚变蛋白.这是一种PEG替代品.具体的癌症治疗方法癌症治疗方法

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