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Selective Prodrug Activation in Cancer Cells Using Protein Switches
Case ID:
C10450
Report of Invention:
8/1/2008
Web Published:
10/7/2014
Unmet Need:
Gene-directed enzyme prodrug therapy (GDEPT; also known as “suicide gene therapy”) is an emerging gene therapy strategy against cancer. A prodrug is systemically administered but only activated in cancer cells that have previously been modified to express an enzyme capable of activating the drug. Yet, the clinical utility of GDEPT to date has been limited by lack of specificity for cancer cells over healthy tissue. Disclosed herein in a novel approach that combines domains of a prodrug-activating enzyme and a cancer cell-specific ligand, respectively, into a single molecular switch. Advantages include:
Novel protein engineering strategy that combines domains of two independent proteins into a single hybrid protein
Allows for selective prodrug internalization and activation only in cancer cells
Enables improved efficacy of chemotherapy treatment whilst reducing side-effects
Technical Details:
Johns Hopkins researchers have developed a novel approach to GDEPT using switches that uses gene delivery to deliver the therapeutic switch gene that can activate the prodrug. The present approach utilizes a targeting strategy distinct from transductional and transcription targeting. Further, it does not necessarily require specific delivery to target cells or activation of the gene in target cells because the catalytic activity that activates the prodrug is preferably regulated at the enzyme level and is preferably activated only in the target cells. Accordingly, the present invention allows methods to efficiently deliver genes to the target cells to be used (methods that may lack cell-specificity), since expression of the therapeutic protein in non-target cells will not result in prodrug activation since the cells lack the signal to activate the enzyme.
Patent Status:
Granted US Patents
8,771,679
and
9,469,841
Associated Publications:
Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16206-11.
Patent Information:
Title
App Type
Country
Serial No.
Patent No.
File Date
Issued Date
Expire Date
Patent Status
Prodrug Activation in Cancer Cells Using Molecular Switches
PCT: Patent Cooperation Treaty
United States
13/059,014
8,771,679
2/14/2011
7/8/2014
8/13/2029
Granted
Direct Link:
https://jhu.technologypublisher.com/technology/16669
Inventors:
Category(s):
Clinical and Disease Specializations, Clinical and Disease Specializations > Oncology, Technology Classifications > Diagnostics > Biomarkers, Technology Classifications > Therapeutic Modalities > Biologics, Technology Classifications > Therapeutic Modalities > Peptides, Technology Classifications > Therapeutic Modalities > Targets, Technology Classifications > Diagnostics, Technology Classifications > Therapeutic Modalities, Technology Classifications > Therapeutic Modalities > Proteins, Technology Classifications > Therapeutic Modalities > Gene Therapies,
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For Information, Contact:
Vera Sampels
vsampel2@jhu.edu
410-614-0300
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