B-cell epitope peptide vaccination targeting dimer interface of epidermal growth factor receptor (EGFR)

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• 作者：Lei Zhu ; Lin Zhao ; Meizhi Wu ; Zhange Chen ; Huangjin Li
• 关键词：EGFR ; epidermal growth factor receptor ; EGF ; epidermal growth factor ; TGF¦Á ; transforming growth factor ¦Á ; MVF ; measles virus fusion protein ; HER-2 ; human epidermal growth factor receptor 2 ; HER-3 ; human epidermal growth factor receptor 3 ; HER-4 ; human e
• 刊名：Immunology Letters
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：153
• 期：1-2
• 页码：33-40
• 全文大小：1031 K

文摘

Epidermal growth factor receptor (EGFR) was the first receptor to be proposed as the target for cancer therapy, however, the anti-EGFR therapy showed a low response rate clinically. Dimerization plays a key role in the activation of EGFR, so targeting the conservative dimer interface probably improve the responses of anti-EGFR clinically. To evoke a high titers of antibodies (Abs) targeting the dimer interface of EGFR in patients, a chimeric peptide, comprising a linear B-cell epitope peptide from the highly conservative ¦Â-hairpin loop of dimer interface of human EGFR (EGFR^237-267) and a ¡®promiscuous¡¯ T_h-cell epitope MVF from the measles virus fusion protein, was constructed. The construct was immunogenic and able to elicit high titers of peptide-specific Abs in both mice and rabbits, while both animals¡¯ EGFRs contain a sequence 100 % homologous to EGFR^237-267. The peptide-specific Abs could recognize and inhibit EGFR over-expressing epithelial cancer cells, such as epidermoid carcinoma A431 and Lewis lung cancer (LLC), furthermore, the binding of the Abs to the native EGFR on the surface of cells was ligand-dependent, which meant that these Abs did target the dimer interface of EGFR as designed, because the exposure of the interface needs ligand binding. The chimeric peptide immunization was able to significantly inhibit the growth of subcutaneously transplanted LLC cells in C57BL6 mice. Therefore, the MVF-EGFR^237-267 construct represents a promising candidate for active anti-EGFR immunotherapy and provides a novel targeting strategy for the anti-EGFR therapy.