| Title | Induction of anti-EGFR immune response with mimotopes identified from a phage display peptide library by panitumumab |
| Authors | Wang, Aidong Cui, Ming Qu, Hong Di, Jiabo Wang, Zaozao Xing, Jiadi Wu, Fan Wu, Wei Wang, Xicheng Shen, Lin Jiang, Beihai Su, Xiangqian |
| Affiliation | Peking Univ, Canc Hosp & Inst, Dept Gastrointestinal Surg 4, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China. Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Ctr Bioinformat, Beijing 100871, Peoples R China. Peking Univ, Canc Hosp & Inst, Dept Gastrointestinal Oncol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China. |
| Keywords | EGFR panitumumab mimotope peptide vaccine GROWTH-FACTOR RECEPTOR METASTATIC COLORECTAL-CANCER GASTRIC-CANCER MONOCLONAL-ANTIBODY CETUXIMAB VACCINATION RESISTANCE THERAPY EPITOPE TUMORS |
| Issue Date | 2016 |
| Publisher | ONCOTARGET |
| Citation | ONCOTARGET.2016,7(46),75293-75306. |
| 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 antiEGFR immunotherapy against cancers. |
| URI | http://hdl.handle.net/20.500.11897/492751 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.12167 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 北京肿瘤医院 生命科学学院 |
