Trends in translational medicine and drug targeting and delivery: new insights on an old concept-targeted drug delivery with antibody-drug conjugates for cancers.
Trends in translational medicine and drug targeting and delivery: new insights on an old concept-targeted drug delivery with antibody-drug conjugates for cancers.
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DOI：
10.1002/jps.23761
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发表时间：
2014-01
影响因子：
3.8
通讯作者：
Chien J
中科院分区：
文献类型：
--
作者：
Ho RJ;Chien J
根据JPS药物递送临床试验数据库（jpharmscidabase.org），注册了37，738、14，104和8，060项临床试验，以评估（1）药物递送技术，（2）生物分子平台，和（3）药物代谢和PK-PD相互作用。这些数字自2012年以来增长了19-24%。在临床测试中的生物分子中，抗体占大多数，约9%携带药物缀合物。大约世纪前，保罗埃利希提出了抗体-药物偶联物或“魔术子弹”的概念。单克隆抗体-药物偶联物Mylotarg于2000年被许可用于治疗癌症，并表现出显著的肝毒性和免疫超敏反应。血浆药物的不稳定性和细菌衍生药物可能是部分原因。抗体-药物偶联化学的进展，对生物系统如何响应抗体-药物偶联物的理解，以及科学家们的不懈努力，使得成功开发出高效和有效的第二代抗体-药物偶联物成为可能。随着Adcetris在2011年和Kadcyla在2013年被批准用于淋巴瘤，癌症反应率的约2至4倍的增益归因于药物缀合物。由于已证实的更高的安全性，更多的抗体-药物缀合物正在开发中。Adcetris和Kadcyla的临床成功带来了希望，即抗体引导的“药物子弹”可能在治愈癌症方面真正“神奇”。
According to the JPS Drug Delivery Clinical Trials Database (jpharmscidatabase.org), 37,738, 14,104, and 8,060 clinical trials are registered to evaluate (1) drug delivery technology, (2) biomolecule platform, and (3) drug metabolism and PK-PD interactions. These numbers represent a 19–24% increase since 2012. Within biomolecules in clinical testing, antibodies constitute the majority and ~9% carry drug conjugates. Paul Ehrlich introduced the antibody-drug conjugate or “magic bullet” concept about a century ago. A monoclonal antibody-drug conjugate Mylotarg was licensed for treating cancer in 2000 and exhibits significant liver toxicity and immune hypersensitivity. Plasma drug instability and a bacterial derived drug may be partly to blame. Progress in antibody-drug conjugation chemistry, understanding how biologic systems respond to antibody-drug conjugates, and unwavering efforts of scientists have enabled successful development of highly potent and effective second-generation antibody-drug conjugates. With the approval of Adcetris for lymphoma in 2011 and Kadcyla in 2013, about a two- to fourfold gain in cancer response rate is attributed to drug conjugates. With a demonstrated higher safety profile, many more antibody-drug conjugates are in development. The clinical success of Adcetris and Kadcyla has raised hope that antibody-guided “drug bullets” may be truly “magical” in leading to a cure for cancer.