Reprogramming urokinase into an antibody-recruiting anticancer agent.
Reprogramming urokinase into an antibody-recruiting anticancer agent.
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DOI：
10.1021/cb200374e
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发表时间：
2012-02-17
影响因子：
4
通讯作者：
Spiegel, David A.
中科院分区：
文献类型：
--
作者：
Jakobsche, Charles E.;McEnaney, Patrick J.;Zhang, Andrew X.;Spiegel, David A.
用于控制或创造人类免疫力的合成化合物有可能彻底改变疾病治疗。受此竞技场挑战的启发，我们在此报道了一种通过靶向尿激酶型纤溶酶原激活物受体（uPAR）靶向转移性癌细胞进行免疫介导破坏的策略。尿激酶型纤溶酶原激活物（uPA）和uPAR在广泛的侵袭性癌细胞的表面上过表达，并且被认为对这些细胞的迁移倾向有实质性贡献。我们方法的关键组成部分是靶向尿激酶受体（ARM-U）的抗体募集分子。该双功能构建体通过选择性地将抗体结合小分子共价连接至尿激酶的活性位点而形成。我们证明，ARM-U能够将抗体导向靶癌细胞的表面，并介导针对多种人类癌细胞系的抗体依赖性细胞吞噬作用（ADCP）和抗体依赖性细胞毒性（ADCC）。我们相信，报告的策略有可能为各种致命的侵袭性癌症提供新的治疗选择。
Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy to target metastatic cancer cells for immune-mediated destruction by targeting the urokinase-type plasminogen activator receptor (uPAR). Urokinase-type plasminogen activator (uPA) and uPAR are overexpressed on the surfaces of a wide range of invasive cancer cells and are believed to contribute substantially to the migratory propensities of these cells. The key component of our approach is an antibody-recruiting molecule that targets the urokinase receptor (ARM-U). This bifunctional construct is formed by selectively, covalently attaching an antibody-binding small molecule to the active site of the urokinase enzyme. We demonstrate that ARM-U is capable of directing antibodies to the surfaces of target cancer cells and mediating both antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) against multiple human cancer cell lines. We believe that the reported strategy has the potential to inform novel treatment options for a variety of deadly, invasive cancers.
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影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
4
作者：
Carlson, Coby B.;Mowery, Patricia;Kiessling, Laura L.
通讯作者：
Kiessling, Laura L.
影响因子：
6.4
作者：
Ertongur, S;Lang, S;Gires, O
通讯作者：
Gires, O
DOI：
10.1016/0268-9499(94)90717-x
发表时间：
1994-01-01
期刊：
FIBRINOLYSIS
影响因子：
--
作者：
DANO, K;BEHRENDT, N;PYKE, C
通讯作者：
PYKE, C
DOI：
10.1073/pnas.162187599
发表时间：
2002-08-06
影响因子：
11.1
作者：
Jessani, N;Liu, YS;Cravatt, BF
通讯作者：
Cravatt, BF