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学科主题: 临床医学
题名:
A novel peptide isolated from a phage display peptide library with trastuzumab can mimic antigen epitope of HER-2
作者: Jiang, BH; Liu, WB; Qu, H; Meng, L; Song, SM; Tao, OY; Shou, CC
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2005-02-11
DOI: 10.1074/jcb.M411047200
卷: 280, 期:6, 页:4656-4662
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: ERBB SIGNALING NETWORK ; BREAST-CANCER ; NEU ONCOGENE ; VACCINE ; PROTEIN ; RECEPTOR ; CELL ; HERCEPTIN ; ANTIBODY
英文摘要:

Trastuzumab, a humanized antibody to HER-2, has been shown to be effective in the treatment of breast cancer in which HER-2 overexpression and metastasis occurs. In our search for an effective mimic epitope of HER-2 binding with trastuzumab and to develop HER-2 peptide vaccine, we screened a phage display 12-mer peptide library with trastuzumab as the target. A mimetic peptide (mimotope) H98 (LLGPYELWELSH) that could specifically recognize trastuzumab was isolated. The DNA encoding peptide H98 was cloned and expressed as the fusion protein GST-H98 in Escherichia coli BL21. The purified GST-H98 could specifically bind to trastuzumab and block the binding of trastuzumab to HER-2 protein. Moreover, H98 could significantly block the function of trastuzumab inhibiting the growth of cancer cells. Mice that were immunized with GST-H98 made specific antibody to H98 as well as to HER-2. In addition, T-cell proliferation occurred in mice immunized with GST-H98. Although no sequence homology was found between H98 and HER-2, through the use of structure analysis we were able to determine that peptide H98 contributed to a conformational epitope of HER-2. Furthermore, we determined that the last two amino acids at the C terminus, and the third together with the fourth amino acid at the N terminus of peptide H98 are critical to the binding of H98 to trastuzumab. As a result, we conclude that peptide H98 has potential for being developed as a HER-2 vaccine for biotherapy of cancer with HER-2 overexpression.

语种: 英语
WOS记录号: WOS:000227096600081
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67245
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China
2.Peking Univ, Sch Oncol, Beijing Inst Canc Res, Dept Biochem & Mol Biol, Beijing 100034, Peoples R China
3.Beijing Canc Hosp, Breast Canc Ctr, Beijing 100036, Peoples R China

Recommended Citation:
Jiang, BH,Liu, WB,Qu, H,et al. A novel peptide isolated from a phage display peptide library with trastuzumab can mimic antigen epitope of HER-2[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2005,280(6):4656-4662.
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