Antibody-drug conjugates for cancer therapy.
Antibody-drug conjugates for cancer therapy.
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DOI：
10.1016/s1470-2045(16)30030-4
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Hassan R
中科院分区：
文献类型：
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作者：
Thomas A;Teicher BA;Hassan R
抗体-药物缀合物是与细胞毒性剂缀合的单克隆抗体。他们使用对肿瘤细胞表面蛋白特异的抗体，因此具有传统药物无法实现的肿瘤特异性和效力。用于癌症治疗的有效抗体-药物缀合物的设计需要选择合适的靶标、针对靶标的单克隆抗体、有效的细胞毒性效应分子以及单克隆抗体与细胞毒性剂的缀合。在过去十年中，所有这些方面都取得了实质性进展，因此监管部门批准了ado-曲妥珠单抗-美坦新偶联物和维布妥昔单抗用于临床。几种有前途的抗体-药物偶联物目前正处于后期临床试验阶段。正在进行的努力集中在确定更好的目标，更有效的细胞毒性有效载荷，并在抗体药物接头技术的进一步改进。对抗体-药物缀合物活性的机制基础的改进的理解将使得能够设计与其他药剂的合理组合疗法，包括免疫疗法。
Antibody–drug conjugates are monoclonal antibodies conjugated to cytotoxic agents. They use antibodies that are specific to tumour cell-surface proteins and, thus, have tumour specificity and potency not achievable with traditional drugs. Design of effective antibody–drug conjugates for cancer therapy requires selection of an appropriate target, a monoclonal antibody against the target, potent cytotoxic effector molecules, and conjugation of the monoclonal antibody to cytotoxic agents. Substantial advances in all these aspects in the past decade have resulted in regulatory approval of ado-trastuzumab emtansine and brentuximab vedotin for clinical use. Several promising antibody–drug conjugates are now in late-phase clinical testing. Ongoing efforts are focused on identifying better targets, more effective cytotoxic payloads, and further improvements in antibody–drug linker technology. Improved understanding of the mechanistic basis of antibody–drug conjugate activity will enable design of rational combination therapies with other agents, including immunotherapy.