Site-Specific Dual Antibody Conjugation via Engineered Cysteine and Selenocysteine Residues.
Site-Specific Dual Antibody Conjugation via Engineered Cysteine and Selenocysteine Residues.
复制标题
DOI：
10.1021/acs.bioconjchem.5b00244
复制
发表时间：
2015-11-18
影响因子：
4.7
通讯作者：
Rader C
中科院分区：
文献类型：
--
作者：
Li X;Patterson JT;Sarkar M;Pedzisa L;Kodadek T;Roush WR;Rader C
与传统的抗体-药物结合物(ADC)相比，定点结合技术能够生产出具有更高治疗指数的均一抗体-药物结合物(ADC)。然而，目前的定点连接方法只能将一种类型的药物结合到单一抗体上。鉴于对当前ADC的获得性耐药性的出现，用不同的药物武装单一抗体可能是开发下一代ADC的一个有吸引力的选择。在这里，我们描述了一种特定位置的双共轭策略，作为双弹头ADC的平台。
Site-specific conjugation technologies enable the production of homogeneous antibody-drug conjugates (ADCs) with improved therapeutic indices compared to conventional ADCs. However, current site-specific conjugation methods can only attach one type of drug to a single antibody. Given the emergence of acquired resistance to current ADCs, arming single antibodies with different drugs may provide an attractive option in the development of next-generation ADCs. Here, we describe a site-specific dual conjugation strategy as a platform for dual warhead ADCs.