Cancer’s Trojan Horse

1. Cancer’s Trojan Horse Student ChE 391 October 3, 2002

2. Overview • Cancer • Folate - a new drug delivery technology • Experimental evidence that folate works • Other possible ways to use folate

3. Cancer • Cancer is second leading cause of death in the U.S. • 1.2 million Americans diagnosed every year - less than half will survive 5 years http://www.endocyte.com/oncology.html

4. http://medlib.med.utah.edu/WebPath/GIHTML/GI067.html

5. Two of the major challenges to increasing survival are finding: 1) Diagnostic drugs that can find cancer before it spreads 2) Therapeutic drugs that can destroy cancer cells without harming healthy cells Cancer http://www.endocyte.com/oncology.html

6. New Drug Delivery Technology • Purdue University and Endocyte, Inc. developed a drug delivery system that attaches anticancer drugs to vitamins http://www.endocyte.com/oncology.html

7. How Folate Works • Folate is a form of water-soluble B vitamin • Cancer cells capture folate more effectively than normal cells • Dr. Philip S. Low of Purdue University said, “Basically, we are using vitamins as Trojan Horses to carry virtually any molecule into a cancer cell.” http://www.endocyte.com/oncology.html

8. How Folate Works

9. How Folate Works • Can be applied to many drugs, including imaging agents, chemotherapy drugs, immuno-modulating agents, liposomes, proteins, and even genes • Spoonful of sugar helps the medicine go down http://www.endocyte.com/oncology.html

10. To Diagnose Folate Cancers • Radioactive imaging agent attached to folate (technetium) • FolateScan administered intravenously • When nuclear imaging shows the folate conjugate concentrated in an unknown mass, that mass has folate receptors and is malignant http://usembassy.state.gov/tokyo/wwwhgl0388.html

11. Folate Studies • In U.S. more than 300,000 people per year diagnosed with a cancer that over-expresses folate receptors http://www.endocyte.com/oncology.html

12. Folate Studies • Immunotherapeutic drugs were linked to folate • Found that tumors could be eliminated in mice without any evidence of toxicity to normal tissues http://www.endocyte.com/oncology.html

13. http://www.endocyte.com/oncology.html

14. Folate Studies • A chemotherapy drug called EC72 linked to folate • Cancer bearing mice that received it lived twice as long as mice treated with the non-targeted drug • No signs of toxicity to normal tissues http://www.endocyte.com/oncology.html

15. http://www.endocyte.com/oncology.html

16. Ovarian Cancer Folate Studies • Proof-of-principle study • Thirty-three women were imaged • Folate successfully targeted the imaging agent to the tumors of all of the women • Human trials for treatment begin soon

17. Advantages of Folate Drug Delivery • Over-expression in cancer cells • Natural substance • Many types of drugs • Folate’s small size (MW 441) http://www.endocyte.com/advantages.html

18. Other methods • Sometimes cancer cells will attach to folate but don’t ingest it rapidly • A “beacon” is attached to the folate • The immune system is primed • Beacon-marked cancer cells attacked Perspective. Research and Inquiry. Purdue University. Summer 2002. Page 12

20. Summary • Folate drug delivery method is “using cancer’s nutritional needs against itself.” (Philip Low) • This “Trojan horse” therapeutic approach increases destruction of cancer cells while decreasing toxicity to healthy cells • Human clinical trials for drug treatment method will begin in November Perspective. Research and Inquiry. Purdue University. Summer 2002. Page 12