Oncotarget

Research Papers:

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

Cuimin Deng, Jiani Xiong, Xiaofan Gu, Xiaoying Chen, Shuifa Wu, Zhe Wang, Duanduan Wang, Jinjin Tu and Jieming Xie _

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Oncotarget. 2017; 8:38568-38580. https://doi.org/10.18632/oncotarget.16930

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Abstract

Cuimin Deng1,*, Jiani Xiong2,*, Xiaofan Gu1, Xiaoying Chen3, Shuifa Wu4, Zhe Wang1, Duanduan Wang5, Jinjin Tu1, Jieming Xie1

1Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian, China

2Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

3Department of Experimental Teaching Center of Basic Medical Science, Fujian Medical University, Fuzhou, Fujian, China

4Department of Pharmacology, The 180th Hospital of PLA, Quanzhou, Fujian, China

5Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

*These authors contributed equally to this work

Correspondence to:

Jieming Xie, email: jmxie@mail.fjmu.edu.cn

Keywords: immunotoxins, nanobody, EGFR, cucurmosin

Received: November 16, 2016     Accepted: March 24, 2017     Published: April 07, 2017

ABSTRACT

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.


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