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. http://www.endocyte.com/oncology.h tml 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

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

5. http://www.endocyte.com/oncology.h tml Cancer 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

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

7. http://www.endocyte.com/oncology.h tml 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.”

8. How Folate Works

9. http://www.endocyte.com/oncology.h tml 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

10. http://usembassy.state.gov/tokyo/ww whgl0388.html 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

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

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

13. http://www.endocyte.com/oncology.h tml

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

15. http://www.endocyte.com/oncology.h tml

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

18. Perspective. Research and Inquiry. Purdue University. Summer 2002. Page 12 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

20. Perspective. Research and Inquiry. Purdue University. Summer 2002. Page 12 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