A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan

• Published in: Journal of immunology research Vol. 2019; no. 2019; pp. 1 - 12
• Main Authors: Zheng, Yiqiong, Yu, Yunzhou, Long, Feng, Pang, Xiaobin, Sun, Zhiwei, Ma, Jinling, Du, Peng, Zeng, Dadi, Wang, Qiong, Yu, Xiaoyan, Wang, Shuang, Zhang, Chang, Qiu, Weiyi, Pang, Bo
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2019; Hindawi; John Wiley & Sons, Inc; Wiley
• Subjects: Antitumor activity; Binding sites; Biological activity; Cancer therapies; Cell growth; Cytotoxicity; Diarrhea; Epidermal growth factor; Epidermal growth factor receptors; FDA approval; Immunoglobulin G; Immunoglobulins; Immunology; Immunotherapy; Irinotecan; Kinases; Libraries; Medical research; Monoclonal antibodies; Overdose; Phages; Proteins; Skin; Targeted cancer therapy; Toxicity; Xenografts; United States > US; Sweden; China
• ISSN: 2314-8861; 2314-7156; 2314-7156
• DOI: 10.1155/2019/3017360

To improve efficacy and minimize toxicity of EGFR inhibition treatment, we developed Ame55, a novel anti-EGFR IgG1 with lower affinity to EGFR than cetuximab (C225) from a human phage library. Ame55 had lower bioactivity than cetuximab in vitro but similar antitumor efficacy as cetuximab in vivo. Moreover, Ame55 was more efficacious than cetuximab in a Lovo cell xenograft tumor model when combined with irinotecan (CPT-11). Ame55 concentrates in the mouse xenograft tumor and has less toxicity than cetuximab in cynomolgus monkeys in an overdose study.