Li Xiuling, Patterson James T, Sarkar Mohosin, Pedzisa Lee, Kodadek Thomas, Roush William R, Rader Christoph
Department of Cell and Molecular Biology, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Bioconjug Chem. 2015 Nov 18;26(11):2243-8. doi: 10.1021/acs.bioconjchem.5b00244. Epub 2015 Jul 24.
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.
位点特异性偶联技术能够生产出与传统抗体药物偶联物(ADC)相比具有更高治疗指数的均质ADC。然而,目前的位点特异性偶联方法只能将一种类型的药物连接到单个抗体上。鉴于目前ADC出现了获得性耐药性,用不同药物武装单个抗体可能为下一代ADC的开发提供一个有吸引力的选择。在这里,我们描述了一种位点特异性双偶联策略,作为双弹头ADC的一个平台。