Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12

Abstract

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%–85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.

Keywords

S492R EGFR ectodomain mutation / colorectal cancer / mAb CH12 / immunnotherapy

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81672724, 81871918, and 81472573), the Supporting Programs of Shanghai Science and Technology Innovation Action Plan (No. 18431902900), the Grant from the State Key Laboratory of Oncogenes and Related Genes (No. 91-17-17), and the Shanghai Municipal Commission of Health and Family Planning (No. 201540213).

Compliance with ethics guidelines

Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, and Hua Jiang declare that they have no conflicts of interest. All procedures followed were in line with the ethical standards of the human laboratory responsibility committee (institutions and countries).

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