Generation of Protease Inhibitory Antibodies by Functional In Vivo Selection.
Generation of Protease Inhibitory Antibodies by Functional In Vivo Selection.
复制标题
通过功能性体内选择产生蛋白酶抑制抗体。
DOI：
10.1007/978-1-0716-3589-6_19
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Ge,Xin
中科院分区：
文献类型：
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作者：
Lee,KiBaek;Ge,Xin
针对蛋白酶表达失调和/或底物蛋白水解异常，单克隆抗体（mab）对致病性蛋白酶的高选择性抑制为治疗包括癌症在内的疾病提供了一种有吸引力的治疗方法。在此，我们报告了一种蛋白酶抑制单抗的功能选择方法，通过三种重组蛋白的周质共表达——感兴趣的蛋白酶、抗体Fab库和修饰的β-内酰胺酶TEM-1。我们通过分离高选择性和有效的抑制人基质金属蛋白酶9 （MMP9）的单抗来验证这种方法。
Targeting dysregulated protease expression and/or abnormal substrate proteolysis, highly selective inhibition of pathogenic proteases by monoclonal antibodies (mAbs) presents an attractive therapeutic approach for the treatment of diseases including cancer. Herein, we report a functional selection method for protease inhibitory mAbs by periplasmic co-expression of three recombinant proteins—a protease of interest, an antibody Fab library, and a modified β-lactamase TEM-1. We validate this approach by isolation of highly selective and potent mAbs inhibiting human matrix metalloproteinase 9 (MMP9).