An insulin growth factor-I/II-neutralizing monoclonal antibody in combination with epidermal growth factor receptor inhibitors potently inhibits tumor cell growth

Guofang Ma; Chengyue Tan; Yaming Shan; Ningyi Shao; Feng Wang; Dimiter S Dimitrov; Liping Wang; Qi Zhao

doi:10.7150/jca.69064

An insulin growth factor-I/II-neutralizing monoclonal antibody in combination with epidermal growth factor receptor inhibitors potently inhibits tumor cell growth

J Cancer. 2022 Mar 21;13(6):1830-1836. doi: 10.7150/jca.69064. eCollection 2022.

Authors

Guofang Ma^{1

2}, Chengyue Tan^{3

4}, Yaming Shan^{1

2}, Ningyi Shao^{3

4}, Feng Wang⁵, Dimiter S Dimitrov⁶, Liping Wang^{1

2}, Qi Zhao^{3

4}

Affiliations

¹ Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, School of Life Sciences; Jilin University, Changchun, Jilin, China.
² Engineering Laboratory for AIDS Vaccine, Jilin Universtiy, Changchun Jilin, China.
³ Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
⁴ MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China.
⁵ Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China.
⁶ Department of Medicine, Center for Antibody Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.

Abstract

The insulin-like growth factors (IGFs), IGF-1 and IGF-II, which bind to the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), have been implicated in the growth, survival, and metastasis of tumor cells. We have previously identified a novel human monoclonal antibody (mAb), m708.5, which neutralizes both human IGF-I and IGF-II, and potently inhibits phosphorylation of the IGF-1R and the IR in breast cancer cells. In this study, m708.5 exhibited very strong synergy with the epidermal growth factor receptor (EGFR) inhibitor gefitinib, and synergy with chemotherapeutic agents in vitro against either neuroblastoma or breast cancer cells. In xenografted models, the combination of m708.5 and gefitinib significantly inhibited LAN-1 cell growth better than single agent alone. Taken together, these results support the clinical development of m708.5 for solid tumors with potential for synergy with chemotherapy and EGFR inhibitors.

Keywords: EGFR; IGF-I; IGF-II; gefitinib; m708.5; monoclonal antibody.