Oncotarget

Research Papers:

Induction of anti-EGFR immune response with mimotopes identified from a phage display peptide library by panitumumab

Aidong Wang, Ming Cui, Hong Qu, Jiabo Di, Zaozao Wang, Jiadi Xing, Fan Wu, Wei Wu, Xicheng Wang, Lin Shen, Beihai Jiang _ and Xiangqian Su

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Oncotarget. 2016; 7:75293-75306. https://doi.org/10.18632/oncotarget.12167

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Abstract

Aidong Wang1,*, Ming Cui1,*, Hong Qu2, Jiabo Di1, Zaozao Wang1, Jiadi Xing1, Fan Wu1, Wei Wu1, Xicheng Wang3, Lin Shen3, Beihai Jiang1, Xiangqian Su1

1Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China

2Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China

3Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China

*These authors have contributed equally to this work

Correspondence to:

Beihai Jiang, email: beihai_jiang@bjmu.edu.cn

Xiangqian Su, email: suxiangqian@bjmu.edu.cn

Keywords: EGFR, panitumumab, mimotope, peptide vaccine

Received: January 01, 2016     Accepted: September 12, 2016     Published: September 21, 2016

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.


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