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一种新型抗 EGFR mAb Ame55,与伊立替康联合使用时,其毒性低于西妥昔单抗,疗效优于西妥昔单抗。

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

机构信息

Antibody Engineering Group, Beijing Biotechnology Institute, 100071 Beijing, China.

Pharmaceutical Institute, Henan University, 475004 Kaifeng, China.

出版信息

J Immunol Res. 2019 Jan 13;2019:3017360. doi: 10.1155/2019/3017360. eCollection 2019.

Abstract

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 but similar antitumor efficacy as cetuximab . 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.

摘要

为了提高 EGFR 抑制治疗的疗效并降低其毒性,我们从人噬菌体文库中开发了一种新型抗 EGFR IgG1 抗体 Ame55,它与 cetuximab(C225)相比对 EGFR 的亲和力较低。Ame55 的生物活性低于 cetuximab,但抗肿瘤疗效与 cetuximab 相似。此外,在与伊立替康(CPT-11)联合使用时,Ame55 在 Lovo 细胞异种移植肿瘤模型中的疗效优于 cetuximab。在过量研究中,Ame55 在小鼠异种移植肿瘤中浓集,并且在食蟹猴中的毒性低于 cetuximab。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab0/6348820/b6ee92797000/JIR2019-3017360.001.jpg

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