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Novel recombinant immunotoxin of EGFR specific nanobody fused with cucurmosin construction and antitumor efficiency in vitro

机译:葫芦菌素融合的EGFR特异性纳米抗体的新型重组免疫毒素体外构建及抗肿瘤作用

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摘要

Epidermal growth factor receptor (EGFR) overexpression is related to the increased aggressiveness, metastases, and poor prognosis in various cancers. In this study, we successfully constructed a new EGFR nanobody-based immunotoxin rE/CUS containing cucurmosin (CUS), The immunotoxin was expressed by prokaryotic system and we obtained a yield of 5 mg protein per liter expression medium. The percentage of it's binding ability totumor cell lines A549, HepG2, SW116, which highly expressed EGFR was 55.6%, 79.6% and 97.1%, respectively, but SW620 was only 4.45%. rE/CUS has the ability to bind A549, HepG2, SW116 cells specifically, and the antigen binding capability was not affected because of extra part of CUS component. The rE/CUS significantly inhibited the cell viability against EGFR over expression tumor cell lines in a dose-and time-dependent manner. Moreover, rE/CUS also induced apoptosis of HepG2 and A549 mightily. Our results demonstrate that rE/CUS is a potential therapeutic strategy for treating EGFR-positive solid tumors.
机译:表皮生长因子受体(EGFR)的过表达与多种癌症的侵略性,转移和预后不良有关。在这项研究中,我们成功地构建了一种新的包含葫芦素(CUS)的基于EGFR纳米抗体的免疫毒素rE / CUS,该免疫毒素通过原核系统表达,每升表达培养基获得5 mg蛋白的产量。它与高表达EGFR的肿瘤细胞系A549,HepG2和SW116的结合能力百分比分别为55.6%,79.6%和97.1%,而SW620仅为4.45%。 rE / CUS具有与A549,HepG2,SW116细胞特异性结合的能力,并且由于CUS组分的过量,抗原结合能力没有受到影响。与表达肿瘤细胞系相比,rE / CUS以剂量和时间依赖性方式显着抑制了针对EGFR的细胞活力。此外,rE / CUS还可能诱导HepG2和A549凋亡。我们的结果表明,rE / CUS是治疗EGFR阳性实体瘤的潜在治疗策略。

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