Stability of the recombinant anti-erbB2 scFv-Fc-interleukin-2 fusion protein and its inhibition of HER2-overexpressing tumor cells | |
Du, Yu-Jia4; Lin, Ze-Min5; Zhao, Ying-Hua3; Feng, Xiu-Ping2; Wang, Chang-Qing2; Wang, Gang2; Wang, Chun-Di2; Shi, Wei2,3; Zuo, Jian-Ping1,5; Li, Fan4 | |
刊名 | INTERNATIONAL JOURNAL OF ONCOLOGY |
2013-02 | |
卷号 | 42期号:2页码:507-516 |
关键词 | anti-erbB2 scFv-Fc-interleukin-2 fusion protein antibody-cytokine fusion protein HER2 overexpression FVB/neu tumor immunotherapy |
ISSN号 | 1019-6439 |
DOI | 10.3892/ijo.2012.1747 |
文献子类 | Article |
英文摘要 | The anti-erbB2 scFv-Fc-IL-2 fusion protein (HFI) is the basis for development of a novel targeted anticancer drug, in particular for the treatment of HER2-positive cancer patients. HFI was fused with the anti-erbB2 antibody and human IL-2 by genetic engineering technology and by antibody targeting characteristics of HFI. IL-2 was recruited to target cells to block HER2 signaling, inhibit or kill tumor cells, improve the immune capacity, reduce the dose of antibody and IL-2 synergy. In order to analyse HFI drug ability, HFI plasmid stability was verified by HFI expression of the trend of volume changes. Additionally, HFI could easily precipitate and had progressive characteristics and thus, the buffer system of the additive phosphate-citric acid buffer, arginine, Triton X-100 or Tween-80, the establishment of a microfiltration, ion exchange, affinity chromatography and gel filtration chromatography-based purification process were explored. HFI samples were obtained according to the requirements of purity, activity and homogeneity. In vivo, HFI significantly delayed HER2 overexpression of non-small cell lung cancer (Calu-3) in human non-small cell lung cancer xenografts in nude mice, and the inhibition rate was more than 60% (P<0.05) in the group treated with 1 mg/kg the HFI dose; HFI significantly inhibited HER2 expression of breast cancer (FVB/neu) trahsgenic mouse tumor growth in 1 mg/kg of the HFI dose group, and in the following treatment the 400 mm(3) tumors disappeared completely. Combined with other HFI test data analysis, HFI not only has good prospects, but also laid the foundation for the development of antibody-cytokine fusion protein-like drugs. |
资助项目 | 'The Key New Drug Creation and Manufacturing' of the Eleventh Five-Year Plan[2009ZX09103-695] |
WOS关键词 | BREAST-CANCER CELLS ; REGULATORY T-CELLS ; TYROSINE KINASE INHIBITOR ; VERSUS-HOST-DISEASE ; IN-VITRO ; MONOCLONAL-ANTIBODIES ; SIGNAL-TRANSDUCTION ; GROWTH ; INTERLEUKIN-2 ; IMMUNOCYTOKINE |
WOS研究方向 | Oncology |
语种 | 英语 |
出版者 | SPANDIDOS PUBL LTD |
WOS记录号 | WOS:000314001000014 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/277754] |
专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
通讯作者 | Li, Fan |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Gene Sci Pharmaceut Co Ltd, Pharmaceut R&D Ctr, Changchun 130012, Peoples R China; 3.Jilin Univ, Coll Life Sci, Minist Educt, Key Lab Mol Enzymol & Engn, Changchun, Peoples R China; 4.Jilin Univ, Norman Bethune Coll Med, Changchun 130021, Peoples R China; 5.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China; |
推荐引用方式 GB/T 7714 | Du, Yu-Jia,Lin, Ze-Min,Zhao, Ying-Hua,et al. Stability of the recombinant anti-erbB2 scFv-Fc-interleukin-2 fusion protein and its inhibition of HER2-overexpressing tumor cells[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2013,42(2):507-516. |
APA | Du, Yu-Jia.,Lin, Ze-Min.,Zhao, Ying-Hua.,Feng, Xiu-Ping.,Wang, Chang-Qing.,...&Wang, Cheng-Zhong.(2013).Stability of the recombinant anti-erbB2 scFv-Fc-interleukin-2 fusion protein and its inhibition of HER2-overexpressing tumor cells.INTERNATIONAL JOURNAL OF ONCOLOGY,42(2),507-516. |
MLA | Du, Yu-Jia,et al."Stability of the recombinant anti-erbB2 scFv-Fc-interleukin-2 fusion protein and its inhibition of HER2-overexpressing tumor cells".INTERNATIONAL JOURNAL OF ONCOLOGY 42.2(2013):507-516. |
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