Rational and combinatorial approaches to engineering a multi-epitopic antagonist of the urokinase receptor

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Abstract/Contents

Abstract
The urokinase receptor (uPAR) has been established as a key driver of cancer metastasis, and an attractive target for therapeutic intervention of disease progression. Various uPAR antagonists have been developed and tested in pre-clinical models of cancer. However, they demonstrated limited efficacy due to their relatively low binding affinity and partial inhibition of uPAR function. To address these limitations, we applied rational and combinatorial engineering methods to generate a high-affinity antagonist capable of simultaneously inhibiting multiple cancer-promoting functions of uPAR. The resulting protein demonstrates potent inhibition of uPA-uPAR binding, as well as enhanced tumor targeting in vivo as proof of concept for further therapeutic development and testing.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2018; ©2018
Publication date 2018; 2018
Issuance monographic
Language English

Creators/Contributors

Author Cherf, Gerald Maxwell
Degree supervisor Cochran, Jennifer R
Thesis advisor Cochran, Jennifer R
Thesis advisor Giaccia, Amato J
Thesis advisor Heilshorn, Sarah
Degree committee member Giaccia, Amato J
Degree committee member Heilshorn, Sarah
Associated with Stanford University, Department of Bioengineering.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Gerald Maxwell Cherf.
Note Submitted to the Department of Bioengineering.
Thesis Thesis Ph.D. Stanford University 2018.
Location electronic resource

Access conditions

Copyright
© 2018 by Gerald Maxwell Cherf
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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