抗体药物偶联物:癌症的靶向药物递送。

Antibody-drug conjugates: targeted drug delivery for cancer.

机构信息

Seattle Genetics, Inc., 21823 30th Drive SE, Bothell, WA 98021, United States.

出版信息

Curr Opin Chem Biol. 2010 Aug;14(4):529-37. doi: 10.1016/j.cbpa.2010.06.170. Epub 2010 Jul 17.

Abstract

The antibody-drug conjugate field has made significant progress recently owing to careful optimization of several parameters, including mAb specificity, drug potency, linker technology, and the stoichiometry and placement of conjugated drugs. The underlying reason for this has been obtained in pre-clinical biodistribution and pharmacokinetics studies showing that targeted delivery leads to high intratumoral free drug concentrations, while non-target tissues are largely spared from chemotherapeutic exposure. Recent developments in the field have led to an increase in the number of ADCs being tested clinically, with 3 in late stage clinical trials: brentuximab vedotin (also referred to as SGN-35) for Hodgkin lymphoma; Trastuzumab-DM1 for breast cancer; and Inotuzumab ozogamicin for non-Hodgkin lymphoma. This review highlights the recent pre-clinical and clinical advances that have been made.

摘要

近年来,由于对几个参数的精心优化,包括单抗特异性、药物效力、连接子技术以及连接药物的化学计量和位置,抗体药物偶联物领域取得了重大进展。这一现象的根本原因是在临床前的生物分布和药代动力学研究中表明,靶向递送导致肿瘤内游离药物浓度升高,而非靶组织基本免受化疗药物暴露。该领域的最新进展导致正在进行临床试验的 ADC 数量增加,其中有 3 个处于晚期临床试验阶段:用于霍奇金淋巴瘤的 Brentuximab Vedotin(也称为 SGN-35);用于乳腺癌的 Trastuzumab-DM1;以及用于非霍奇金淋巴瘤的 Inotuzumab Ozogamicin。本文综述了最近在临床前和临床方面取得的进展。

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