Oncotarget

Research Papers:

Characterization of 7A7, an anti-mouse EGFR monoclonal antibody proposed to be the mouse equivalent of cetuximab

Xuzhi He _, Jazmina L. Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K. Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson and James W. Wells

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Oncotarget. 2018; 9:12250-12260. https://doi.org/10.18632/oncotarget.24242

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Abstract

Xuzhi He1,*, Jazmina L. Cruz1,*, Shannon Joseph1,2, Nicola Pett1, Hui Yi Chew2, Zewen K. Tuong1, Satomi Okano2, Gabrielle Kelly1, Margaret Veitch1, Fiona Simpson1,2,# and James W. Wells1,#

1The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia

2Queensland Head and Neck Cancer Centre, Princess Alexandra Hospital, Brisbane, QLD, Australia

*These authors share first authorship of this work

#These authors share senior authorship of this work

Correspondence to:

James W. Wells, email: j.wells3@uq.edu.au

Fiona Simpson, email: f.simpson@uq.edu.au

Keywords: 7A7; cetuximab; mouse epidermal growth factor receptor; IgG1

Received: October 13, 2017     Accepted: December 05, 2017     Published: January 13, 2018

ABSTRACT

The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer. However, only 15-20% patients benefit from this drug, thus new strategies to improve cetuximab efficiency are required. We aimed to develop a reliable and easy preclinical mouse model to evaluate the efficacy of EGFR-targeted antibodies and examine the immune mechanisms involved in tumour regression. We selected an anti-mouse EGFR mAb, 7A7, which has been reported to be “mouse cetuximab” and to exhibit similar properties to its human counterpart. Unfortunately, we were unable to reproduce previous results obtained with the 7A7 mAb. In our hands, 7A7 failed to recognize mouse EGFR, both in native and reducing conditions. Moreover, in vivo administration of 7A7 in an EGFR-expressing HPV38 tumour model did not have any impact on tumour regression or animal survival. We conclude that 7A7 does not recognize mouse EGFR and therefore cannot be used as the mouse equivalent of cetuximab use in humans. As a number of groups have spent effort and resources with similar issues we feel that publication is a responsible approach.


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