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A novel immunotoxin-rCCK8PE38 targeting of CCK-R overexpressed colon cancers 期刊论文

编号：

808be837-077f-4532-a340-a44d557384b1
作者：

Gao, Shiqi#^[1]Song, Jie#*^[1,2]Chen, Fengge^[1];Wang, Quan^[3];Liu, Xilin(柳溪林)^[4]Ren, Honglin^[1];Li, Yansong^[1];Meng, Xingyu^[1];Zhou, Yu^[1];Lu, Shiying^[1];Hu, Pan^[1];Tong, Weihua^[3];Liu, Zengshan(柳增善)*^[1]
语种：

英文
期刊：

JOURNAL OF DRUG TARGETING ISSN：1061-186X 2015 年 23 卷 5 期 (462 - 468) ; JUN
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关键词：

CCKR colon cancer rCCK8PE38 recombinant immunotoxin Pseudomonas exotoxin A
摘要：

Background: Cholecystokinin (CCK) receptors are overexpressed in numerous human cancers, such as pancreatic, colon and gastric cancers. Previous studies have shown that the specific receptor-binding property of CCK for CCK receptors (CCKRs) can be exploited to produce immunotoxins (ITs) that target cancer cells overexpressing CCK receptors.
Purpose: Construct a new IT-targeting CCKR-overexpressing colon cancers.
Methods: To construct the CCKR-targeted IT, a reverse CCK8 peptide was fused with a modified 38-kDa truncated form of the Pseudomonas exotoxin (PE38KDEL). An efficient immunoaffinity purification procedure was used to produce a PE38-based IT. Several analyses, including CCK8 competition and indirect immunofluorescence assays, were performed to confirm the interaction between rCCK8 and CCKR. After cytotoxic assays on several cell lines, the antitumor activity of the new IT was detected in nude mice.
Results: The rCCK8PE38 IT showed specific cytotoxicity for two colon cancer cell lines and one gastric cancer cell line. After purification, 18-26mg of pure rCCK8PE38 per 1 L of culture was obtained. Purified rCCK8PE38 showed high cytotoxicity in colon cancer cell lines with IC50 values of 0.8-3.5 ng/mL. The results of the CCK8 competition and indirect immunofluorescence assays showed that rCCK8 had a specific interaction with CCKR. Nude mice inoculated with HCT-8 tumor xenografts were treated with rCCK8PE38, which efficiently decreased the tumor size in those mice.
Conclusions and discussion: All of these data suggest that rCCK8PE38 has potential as a new immunotherapy agent. Furthermore, the results of this study further support the high value of the immunoaffinity method for IT purification procedures.
推荐引用方式
GB/T 7714：

Gao Shiqi,Song Jie,Chen Fengge, et al. A novel immunotoxin-rCCK8PE38 targeting of CCK-R overexpressed colon cancers [J].JOURNAL OF DRUG TARGETING,2015,23(5):462-468.
APA：

Gao Shiqi,Song Jie,Chen Fengge,Wang Quan,&Liu Zengshan.(2015).A novel immunotoxin-rCCK8PE38 targeting of CCK-R overexpressed colon cancers .JOURNAL OF DRUG TARGETING,23(5):462-468.
MLA：

Gao Shiqi, et al. "A novel immunotoxin-rCCK8PE38 targeting of CCK-R overexpressed colon cancers" .JOURNAL OF DRUG TARGETING 23,5(2015):462-468.
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