Seattle Genetics, Bothell, Washington, USA.
Nat Biotechnol. 2012 Jul 10;30(7):631-7. doi: 10.1038/nbt.2289.
Progress has been made recently in developing antibody-drug conjugates (ADCs) that can selectively deliver cancer drugs to tumor cells. In principle, the idea is simple: by attaching drugs to tumor-seeking antibodies, target cells will be killed and nontarget cells will be spared. In practice, many parameters needed to be addressed to develop safe and effective ADCs, including the expression profiles of tumor versus normal tissues, the potency of the drug, the linker attaching the drug and placement of the drug on the antibody, and the pharmacokinetic and stability profiles of the resulting ADC. All these issues had been taken into account in developing brentuximab vedotin (Adcetris), an ADC that recently received accelerated approval by the US Food and Drug Administration for the treatment of relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Research is under way to extend the applications of brentuximab vedotin and to advance the field by developing other ADCs with new linker and conjugation strategies.
最近在开发抗体药物偶联物(ADC)方面取得了进展,这种 ADC 可以将癌症药物选择性递送到肿瘤细胞。原则上,这个想法很简单:通过将药物连接到靶向肿瘤的抗体上,目标细胞将被杀死,而非目标细胞将被保留。实际上,为了开发安全有效的 ADC,需要解决许多参数问题,包括肿瘤与正常组织的表达谱、药物的效力、连接药物的接头以及药物在抗体上的位置,以及由此产生的 ADC 的药代动力学和稳定性特征。在开发 Brentuximab vedotin(Adcetris)时,已经考虑到了所有这些问题,这种 ADC 最近获得了美国食品和药物管理局的加速批准,用于治疗复发性霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤(ALCL)。目前正在研究扩大 Brentuximab vedotin 的应用范围,并通过开发具有新接头和偶联策略的其他 ADC 来推进这一领域。
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