Li Xiuling, Nelson Christopher G, Nair Rajesh R, Hazlehurst Lori, Moroni Tina, Martinez-Acedo Pablo, Nanna Alex R, Hymel David, Burke Terrence R, Rader Christoph
Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Cell Chem Biol. 2017 Apr 20;24(4):433-442.e6. doi: 10.1016/j.chembiol.2017.02.012. Epub 2017 Mar 16.
Selenomabs are engineered monoclonal antibodies with one or more translationally incorporated selenocysteine residues. The unique reactivity of the selenol group of selenocysteine permits site-specific conjugation of drugs. Compared with other natural and unnatural amino acid and carbohydrate residues that have been used for the generation of site-specific antibody-drug conjugates, selenocysteine is particularly reactive, permitting fast, single-step, and efficient reactions under near physiological conditions. Using a tailored conjugation chemistry, we generated highly stable selenomab-drug conjugates and demonstrated their potency and selectivity in vitro and in vivo. These site-specific antibody-drug conjugates built on a selenocysteine interface revealed broad therapeutic utility in liquid and solid malignancy models.
硒代单克隆抗体是一种工程化单克隆抗体，含有一个或多个经翻译整合的硒代半胱氨酸残基。硒代半胱氨酸的硒醇基团具有独特的反应活性，可实现药物的位点特异性偶联。与用于生成位点特异性抗体-药物偶联物的其他天然和非天然氨基酸及碳水化合物残基相比，硒代半胱氨酸的反应活性特别高，能够在接近生理条件下进行快速、单步且高效的反应。通过定制的偶联化学方法，我们制备出了高度稳定的硒代单克隆抗体-药物偶联物，并在体外和体内证明了它们的效力和选择性。这些基于硒代半胱氨酸界面构建的位点特异性抗体-药物偶联物在液体和实体恶性肿瘤模型中显示出广泛的治疗用途。
