title: B-cell epitope peptide vaccination targeting dimer interface of epidermal growth factor receptor (EGFR).
abstract: 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 β-hairpin loop of dimer interface of human EGFR (EGFR237-267) and a 'promiscuous' Th-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 EGFR237-267. 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-EGFR237-267 construct represents a promising candidate for active anti-EGFR immunotherapy and provides a novel targeting strategy for the anti-EGFR therapy.
authors.affiliation: Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, College of Life Science and Biopharmaceutical, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Meizhi
authors.initials: M
authors.lastname: Wu
authors.forename: Zhange
authors.initials: Z
authors.lastname: Chen
authors.forename: Huangjin
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D019281:Dimerization; D004789:Enzyme Activation; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D014611:Vaccination
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D066246:ErbB Receptors
keywords: B-cell epitope; Dimerization; ECD; EGF; EGFR; HER-2; HER-3; HER-4; MVF; TGFα; Vaccine; epidermal growth factor; epidermal growth factor receptor; extracellular domain.; human epidermal growth factor receptor 2; human epidermal growth factor receptor 3; human epidermal growth factor receptor 4; measles virus fusion protein; transforming growth factor α