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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

融合粒酶B的HPV16E7亲和素组成的亲和素在体外和体内对宫颈癌的靶向生物学效应。

卷 21, 期 3, 2021

发表于: 07 December, 2020

页: [232 - 243] 页: 12

弟呕挨: 10.2174/1568009620666201207145720

价格: $65

摘要

背景：人类乳头瘤病毒（HPV16）的高危16型与50％的子宫颈癌相关，目前尚缺乏可靠的靶向治疗方法。 HPV早期蛋白7（E7）是负责细胞恶性转化的癌蛋白。在我们之前的工作中，开发了针对HPV16E7（ZHPV16E7）的高度特异性的亲和体。目的：为改善靶向治疗效果，本研究制备了由ZHPV16E7与颗粒酶B（GrB）融合的抗毒素，即ZHPV16E7-GrB，并对其在体内外的靶向作用进行了评价。 方法：ZHPV16E7-GrB融合蛋白是在原核表达系统中产生的。 ZHPV16E7-GrB与HPV16E7的靶向结合特性已通过宫颈癌细胞系中的免疫荧光测定（IFA），临床样本中宫颈癌组织的免疫组织化学测定（IHA）以及荷瘤小鼠的近红外成像得以证实。进一步评估了对体外子宫颈癌细胞和体内荷瘤小鼠的抗肿瘤作用。 结果：在大肠杆菌中产生了一个34 kDa的ZHPV16E7-GrB融合蛋白，并显示出相应的免疫反应性。 IFA显示ZHPV16E7-GrB与HPV16阳性TC-1和SiHa细胞特异性结合。 IHA显示ZHPV16E7-GrB还与HPV16阳性临床组织标本特异性结合。另外，近红外成像结果表明ZHPV16E7-GrB在肿瘤组织中富集。此外，ZHPV16E7-GrB亲和素和ZHPV16E7亲和体（无GrB）均显着降低了子宫颈癌细胞的体外和体内荷瘤小鼠的增殖，并且ZHPV16E7-GrB的抗增殖作用高于ZHPV16E7的亲和体。 结论：通过将亲和体与GrB偶联而获得的亲和毒素是一种有前途的靶向治疗剂，具有靶向亲和体和GrB细胞毒素的双重优势。

关键词: HPV 16型，早期蛋白7，亲和体，颗粒酶B，宫颈癌，有针对性的疗效。

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