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- Title
Re-engineering the Immune Response to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor.
- Authors
Rullo, Anthony F.; Fitzgerald, Kelly J.; Muthusamy, Viswanathan; Liu, Min; Yuan, Cai; Huang, Mingdong; Kim, Minsup; Cho, Art E.; Spiegel, David A.
- Abstract
Developing selective strategies to treat metastatic cancers remains a significant challenge. Herein, we report the first antibody-recruiting small molecule (ARM) that is capable of recognizing the urokinase-type plasminogen activator receptor (uPAR), a uniquely overexpressed cancer cell-surface marker, and facilitating the immune-mediated destruction of cancer cells. A co-crystal structure of the ARM-U2/uPAR complex was obtained, representing the first crystal structure of uPAR complexed with a non-peptide ligand. Finally, we demonstrated that ARM-U2 substantially suppresses tumor growth in vivo with no evidence of weight loss, unlike the standard-of-care agent doxorubicin. This work underscores the promise of antibody-recruiting molecules as immunotherapeutics for treating cancer.
- Subjects
METASTASIS; CANCER immunotherapy; UROKINASE; SMALL molecules; PLASMINOGEN activators; CANCER treatment; THERAPEUTICS
- Publication
Angewandte Chemie, 2016, Vol 128, Issue 11, p3706
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201510866