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首个基于铂(II)的金属有机连接子技术(Lx®),用于抗体药物偶联物(ADC)的即插即用开发。

First platinum(II)-based metal-organic linker technology (Lx®) for a plug-and-play development of antibody-drug conjugates (ADCs).

机构信息

a Research and Development Department, LinXis BV , Amsterdam , The Netherlands.

b Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit , Amsterdam , The Netherlands.

出版信息

Expert Opin Drug Deliv. 2019 Aug;16(8):783-793. doi: 10.1080/17425247.2019.1645118. Epub 2019 Jul 24.

Abstract

: Compared to the antibody and drug components of an ADC, the linker part has been somewhat neglected. However, its importance for the reduction of failures in ADC approvals is increasingly recognized. Next of being a stable glue between drug and antibody, an ideal linker should improve the manufacturability and widen the therapeutic window of ADCs. : The biopharmaceutical company LinXis started an ADC development program in which platinum(II) is the key element of the first metal-organic linker. The cationic complex [ethylenediamineplatinum(II)], herein called '®', is used successfully for conjugation of drugs to antibodies. : Based on lessons learned from ADC development, linker technology fulfills most of the desirable linker characteristics. allows large-scale cost-effective manufacturing of ADCs via a straightforward two-step 'plug-and-play' process. First clinical candidate trastuzumab--auristatin F shows favorable preclinical safety as well as outstanding tumor targeting performance and therapeutic efficacy.

摘要

与 ADC 的抗体和药物成分相比,连接子部分有些被忽视。然而,其对于减少 ADC 批准失败的重要性日益得到认可。作为药物和抗体之间的稳定连接物,理想的连接子应提高 ADC 的可制造性并拓宽治疗窗口。

生物制药公司 LinXis 启动了 ADC 开发计划,其中铂(II)是第一个金属有机连接子的关键元素。阳离子配合物[乙二胺铂(II)],在此称为“®”,成功用于将药物连接到抗体上。

基于从 ADC 开发中吸取的经验教训,连接子技术满足了大多数理想的连接子特性。它允许通过简单的两步“即插即用”工艺进行大规模、具有成本效益的 ADC 制造。第一个临床候选药物曲妥珠单抗-auristatin F 表现出良好的临床前安全性以及出色的肿瘤靶向性能和治疗效果。

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