title: Induction of anti-EGFR immune response with mimotopes identified from a phage display peptide library by panitumumab.
abstract: The epidermal growth factor receptor (EGFR) is overexpressed in several epithelial tumors. Anti-EGFR humanized monoclonal antibodies, cetuximab and panitumumab, in combination with chemotherapy have improved the prognosis for patients with wild-type RAS tumors. To identify mimotopes of EGFR and develop mimotope-based EGFR vaccines, we screened a phage display peptide library with panitumumab. Two EGFR mimotopes P19 and P26, which could be recognized by panitumumab specifically, were isolated. To enhance the immune responses, we generated recombinant proteins of P19 or P26 fused to a heat-shock cognate protein 70 (Hsc70), and evaluated the efficacy of Hsc70-P19 and Hsc70-P26 as vaccines in vivo. Immunization with Hsc70-P19 or Hsc70-P26 fusion protein stimulated the immune system to produce specific antibodies against peptides as well as EGFR. Moreover, antibodies elicited against mimotopes could induce antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and inhibit the proliferation of EGFR-overexpressing A431 cells. Treatment with Hsc70-P19 and Hsc70-P26 significantly reduced tumor growth in BALB/c transplantable lung cancer models. Although there was no sequence homology between the phage-derived peptides and EGFR by alignments, both peptides mimic the conformational structure of EGFR binding to panitumumab. In conclusion, the mimotopes we identified from phage display peptide library could be promising candidate vaccines for active anti-EGFR immunotherapy against cancers.
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cui
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Di
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Jiadi
authors.initials: J
authors.lastname: Xing
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xicheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Beihai
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Su
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D061505:Cell Surface Display Techniques; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D008958:Models, Molecular; D000077544:Panitumumab; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; D000077544:Panitumumab; D066246:ErbB Receptors
keywords: EGFR; mimotope; panitumumab; peptide vaccine