1. Is Immunotherapy the Future of Cancer Treatment? By: Uma Kantheti RISE Mentor: Dr. Doll

2. Review: Older Therapies Surgery Physically removing a tumor from a patient Radiation Therapy Using ionizing radiation to kill localized tumors Chemotherapy A class of drugs that kills rapidly dividing cells in the body

3. Small Molecule Target Therapy Type of medical that focuses in designing therapies that target specific molecular alterations Successful drugs are Gleevec and Zelboraf (tyrosine kinase inhibitors)

4. Setbacks Low response rates Tumors can develop resistance to the drug Target therapy works only if the drug’s target is found in all tumor cells Sub-clonal mutations are hard to account for in small molecule target therapy

5. Immunotherapy Generating an immune response against cancer cells Creates durable responses across a diverse spectrum of malignancies A successful class of immunotherapy drugs are checkpoint blockade drugs

6. Historical Perspective William Coley- Father of modern immunotherapy Injected Streptococcus bacteria into Zola’s tumor Liquefied and disappeared after two weeks

7. Checkpoint Blockade Drugs

8. PD-1 and PD-L1 Combination therapies are more effective. PD-1 works best in conjunction with CTLA-4

9. Is immunotherapy really more successful that other cancer treatments?

10. Is immunotherapy the most successful cancer treatment? Hard to say because most of the drugs are in stage III clinical trials The drugs that are on the market do have much higher remission rates that any other form of cancer therapy Most scientific papers discuss “the promising potential” of different immunosuppressive pathways Pharmaceutical companies have chosen to move their cancer research into this form of treatment

12. Going large with biologics 20 th century was the era of the small molecule (a relatively simple compound) Biologics are drugs that consist of giant molecules Manufactured in side animal cells or microorganisms Biologics provided 22% of the big pharmaceutical companies’ sales in 2013 Will rise to 32% by year 2023

14. Conclusion Cancer is diverse and exists in hundreds of different forms In order to treat the spectrum of different cancer- immune environments, Anti-PD-1 will probably form the foundation for many future cancer treatments New immune checkpoint blockade pathways that complement PD-1 hold great promise to improve responses in tumors

15. References Schmitt MW, Loeb LA, Salk JJ. 2015. The influence of subclonal resistance mutation on targeted cancer therapy. Nat Clin Pract Oncol 10.1038/nrclinonc.2015.175. Symth MJ, Ngiow SF, Ribas A, Teng MWL. 2016. Combination cancer immunotherapies tailored to the tumor microenvironment. Nat Clin Pract Oncol 13: 143-155. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. 2016. The future of cancer treatment immunomodulation, CAR and combination immunotherapy. Nat Clin Pract Oncol 10.1038/nrclinonc.2016.25. Egen JG, Kuhns MS, Allison JP. 2002. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 3:611-618. Hoos A. 2016. Development of immuno-oncology drugs – from CTLA4 to PD1 to the next generations. Nature 10.1038/nrd.2015.35. Johnson DB. Melanoma-specific MHC-II expression represents a tumor-autonomous phenomenon and predicts response to anti-PD-1/PD-L1 therapy. Nature 7:10582.