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

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. Mo...

Full description

Saved in:
Bibliographic Details
Main Authors: Weiyi Qiu, Chang Zhang, Shuang Wang, Xiaoyan Yu, Qiong Wang, Dadi Zeng, Peng Du, Jinling Ma, Yiqiong Zheng, Bo Pang, Yunzhou Yu, Feng Long, Xiaobin Pang, Zhiwei Sun
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/3017360
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849399837744693248
author Weiyi Qiu
Chang Zhang
Shuang Wang
Xiaoyan Yu
Qiong Wang
Dadi Zeng
Peng Du
Jinling Ma
Yiqiong Zheng
Bo Pang
Yunzhou Yu
Feng Long
Xiaobin Pang
Zhiwei Sun
author_facet Weiyi Qiu
Chang Zhang
Shuang Wang
Xiaoyan Yu
Qiong Wang
Dadi Zeng
Peng Du
Jinling Ma
Yiqiong Zheng
Bo Pang
Yunzhou Yu
Feng Long
Xiaobin Pang
Zhiwei Sun
author_sort Weiyi Qiu
collection DOAJ
description 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.
format Article
id doaj-art-a487f8e37a354c5f832b36fd8d4422fc
institution Kabale University
issn 2314-8861
2314-7156
language English
publishDate 2019-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-a487f8e37a354c5f832b36fd8d4422fc2025-08-20T03:38:14ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/30173603017360A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with IrinotecanWeiyi Qiu0Chang Zhang1Shuang Wang2Xiaoyan Yu3Qiong Wang4Dadi Zeng5Peng Du6Jinling Ma7Yiqiong Zheng8Bo Pang9Yunzhou Yu10Feng Long11Xiaobin Pang12Zhiwei Sun13Antibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaJoinn Laboratories (China), Co. Ltd, 100176 Beijing, China301 Hospital, 100853 Beijing, ChinaClinical Laboratory, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, 100053 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaPharmaceutical Institute, Henan University, 475004 Kaifeng, ChinaAntibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, ChinaTo 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.http://dx.doi.org/10.1155/2019/3017360
spellingShingle Weiyi Qiu
Chang Zhang
Shuang Wang
Xiaoyan Yu
Qiong Wang
Dadi Zeng
Peng Du
Jinling Ma
Yiqiong Zheng
Bo Pang
Yunzhou Yu
Feng Long
Xiaobin Pang
Zhiwei Sun
A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan
Journal of Immunology Research
title A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan
title_full A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan
title_fullStr A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan
title_full_unstemmed A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan
title_short A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan
title_sort novel anti egfr mab ame55 with lower toxicity and better efficacy than cetuximab when combined with irinotecan
url http://dx.doi.org/10.1155/2019/3017360
work_keys_str_mv AT weiyiqiu anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT changzhang anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT shuangwang anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT xiaoyanyu anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT qiongwang anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT dadizeng anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT pengdu anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT jinlingma anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT yiqiongzheng anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT bopang anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT yunzhouyu anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT fenglong anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT xiaobinpang anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT zhiweisun anovelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT weiyiqiu novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT changzhang novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT shuangwang novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT xiaoyanyu novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT qiongwang novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT dadizeng novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT pengdu novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT jinlingma novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT yiqiongzheng novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT bopang novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT yunzhouyu novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT fenglong novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT xiaobinpang novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan
AT zhiweisun novelantiegfrmabame55withlowertoxicityandbetterefficacythancetuximabwhencombinedwithirinotecan