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

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

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)

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

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

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

Checkpoint Blockade Drugs

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

Is immunotherapy really more successful that other cancer treatments?

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

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

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

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