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Technology Background 

Eric J. Sorscher and William B. Parker discovered that the expression of E. coli purine nucleoside phosphorylase (E. coli PNP) in a small percentage of the cells in a tumor can be exploited to selectively kill the entire tumor (Figure 1).  In these studies E. coli PNP converts fludarabine phosphate (F-araAMP), a chemotherapeutic agent already in clinical use, to fluoroadenine, a very potent tumor killing agent (Figure 2).   Fludarabine phosphate is currently approved by the FDA for the treatment of certain hematologic malignancies, but is not used in the treatment of solid tumors.  The selective expression of E. coli PNP in the cells of solid tumors can significantly expand the spectrum of anticancer activity of this agent.   Furthermore, fluoroadenine is active against both proliferating and nonproliferating tumor cells, and therefore, unlike other anti-tumor agents, this treatment strategy can kill the non-proliferating component of solid tumors. 

Cancer targets 

The treatment strategy is effective against all tumor types, and is only dependent upon the ability to selectively deliver E. coli purine nucleoside phosphorylase to the tumors. 

Unique Properties of the E. coli PNP System 

• Targets all solid tumors
• E. coli PNP selectively activates a known, FDA-approved anti-tumor agent, fludarabine phosphate
• Effectiveness proven in multiple mouse models of human cancers (ovarian, lymphoma, colon, brain, liver, prostate, pancreatic, etc)
• Safety/pharmacology demonstrated in numerous preclinical studies
• Drug delivery and chemotherapeutic components previously evaluated in human subjects and are known to be safe
• Replaces the use of radiation therapy with a less toxic, less debilitating therapeutic strategy
• Novel mechanism of cell kill
• Multi-billion dollar market potential

Figure 1

Effect of F-araAMP on D54 human tumors in which

2.5, 5, or 10 percent of the cells express E. coli PNP 

Figure 2

Schematic showing the activation of F-araAMP to fluoroadenine

by enzymes in the blood and E. coli PNP in tumor cells 

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Last modified: April 07, 2008