Reprogramming urokinase into an antibody-recruiting anticancer agent.

Abstract:

: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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Jakobsche CE,McEnaney PJ,Zhang AX,Spiegel DA

doi

10.1021/cb200374e

subject

Has Abstract

pub_date

2012-02-17 00:00:00

pages

316-21

issue

2

eissn

1554-8929

issn

1554-8937

journal_volume

7

pub_type

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