1. Immunotherapy Sara Engh & Tenzin Yiga

2. Role of the Immune system ➔ Defends against pathogens such as bacteria, fungi, and viruses that enter the body ➔ Responds to antigens on the surface of materials to relay whether they are foreign or not ➔ Cancer cells have antigens that are only slightly different from normal cells and can be missed ➔ “Cancer cells are less like soldiers of an invading army and more like traitors within the ranks of the human cell population” (American Cancer Society, 2014) http://www.airheads1.com/o2_for_immune_system.php

3. What is Immunotherapy ➔ Cancer immunotherapy is a modality that uses a person’s own immune system to help combat diseases such as cancer ◆ Uses man-made immune system proteins in the lab or materials made by the body ➔ AKA: biotherapy ➔ Still not clear how the process actually helps treat cancer but is thought to either slow/stop tumor growth or increase the body’s natural ability to find and eliminate cancerous cells

4. Types of Immunotherapies ➔ Monoclonal antibodies ➔ Non-specific immunotherapies ➔ Cancer vaccines http://www.huffingtonpost.com/2013/11/04/provenge-cancer-vaccine_n_4181851.html

5. Monoclonal antibodies (mAbs) ➔ Monoclonal antibodies are lab-made and injected intravenously into the patient (Examples of FDA approved mAbs: Herceptin, Rituxan, Campath…) ➔ Target specific proteins on the surface of cancer cells or supporting cells ➔ Outcomes ◆ Assist immune system to destroy cancer cells, prevent growth, deliver radiation, diagnose cancers

6. Non-specific immunotherapies ➔ 2 most common non-specific immunotherapies ◆ Interferons ● Help immune system by potentially slowing down cancer growth ◆ Interleukins ● Help immune system to produce more cells that fight off cancer cells

7. Cancer Vaccines ➔ Vaccines expose the body to the antigen of a certain disease or pathogen, which then trains the immune system to recognize the material ➔ Prevention vaccines ◆ pts with no symptoms (proactive) ◆ i.e. HPV vaccine (Gardasil, Cervarix) ➔ Treatment vaccines ◆ helps immune system fight certain cancers by training it to recognize the cancer cells ◆ i.e. Provenge is the only approved treatment vaccine in the U.S. (metastatic prostate cancer)

8. Benefits and Side Effects of Immunotherapy ➔ Fewer harsh side effects compared to chemotherapy and radiation therapy ◆ Possible side effects of immunotherapy are fever, chills, weakness, headache, nausea, vomiting, diarrhea, low BP, and rashes (American Cancer Society, 2014) ➔ Does not cause secondary malignancies ➔ Can increase remission period or decrease the chance of recurrence ◆ Memory cells in the immune system ◆ GP2 vaccine has shown to reduce recurrence rates in breast cancer patients by 57% (MD Anderson Cancer Center, 2014)

9. Types of Cancers Immunotherapy is Used for ➔ Prostate Cancer (cell-based immunotherapy) ◆ Provenge, approved by the FDA in 2010 ◆ Uses patient’s own WBC, most of which are dendritic and infuses them with the antigen prostatic acid phosphatase (PAP) and signaling factor that helps with maturation ◆ extends survival rates by several months (American Cancer Society, 2014) ➔ Melanoma (cytokine immunotherapy) ◆ 1998, the FDA approved interleukin-2 (IL-2) to help treat advanced melanoma and another agent Yervoy became the first proven immunotherapy agent to help extend the life of metastatic patients by 1- 2 years in 2011 (Cancer Research Institute, 2014) http://www.fightcancerwithimmunotherapy.com/Immunoth erapyAndCancer/StateOfCancerImmunotherapy.aspx

10. Immunotherapy Research ➔ The FDA has just granted a Breakthrough Therapy Designation to the pharmaceutical company, Roche, for its promising MPDL3280A (anti-PDL1) immunotherapy used to treat certain types of non-small cell lung cancer (NSCLC) (Drug Discovery & Development, 2015) ➔ Leukemia (Breakthrough Therapy) Chimeric antigen receptor (CAR) T cell therapy is pending approval from the FDA, clinical trials have been very effective. One trial in June of 2011, Acute Lymphoblastic Leukemia treatment results obtained 100% remissions in children and 90% in adults (Cancer Research Institute, 2014) ➔ Immune Checkpoint Inhibitors - blocks the immune checkpoint protein which allows the immune system to recognize the tumor and initiate an immune response ◆ MD Anderson Medical Center developed an antibody, anti-CTLA-4, to block this protein ◆ Study done on metastatic renal cell carcinoma and has shown to cause tumor regression (Hale, 2014)

11. References Cancer Immunotherapy. (2014, December 8). In American Cancer Society. Retrieved February 16, 2014 from http://www.cancer.org/acs/groups/cid/documents/webcontent/003013-pdf.pdfhttp://www.cancer.org/acs/groups/cid/documents/webcontent/003013-pdf.pdf Collins, S. (2014, November 4). Immunotherapy Brings New Hope to Cancer Fight. In WebMD. Retrieved February 16, 2015 from http://www.webmd.com/cancer/news/20141104/immunotherapy-brings-new-hope-cancer-fight http://www.webmd.com/cancer/news/20141104/immunotherapy-brings-new-hope-cancer-fight FDA Grants Breakthrough Therapy Designation to Roche's Lung Cancer Immunotherapy. (2015, February). In Drug Discovery & Development. Retrieved February 16, 2015 from http://www.dddmag.com/news/2015/02/fda-grants-breakthrough-therapy-designation-roches-lung-cancer-immunotherapy http://www.dddmag.com/news/2015/02/fda-grants-breakthrough-therapy-designation-roches-lung-cancer-immunotherapy Melanoma. (2014, August). In Cancer Research Institute. Retrieved February 17, 2015 from http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/melanoma Novel Immunotherapy Vaccine Decreases Recurrence in HER2 Positive Breast Cancer Patients. (2014, September 5). In MD Anderson Cancer Center. Retrieved February 17, 2015, from http://www.mdanderson.org/newsroom/news-releases/2014/vaccine-decreases-reoccurence-her2-breast-cancer.html Oxygen for the Immune System. (2014). In Airheads. Retrieved February 17, 2015, from http://www.airheads1.com/o2_for_immune_system.phphttp://www.airheads1.com/o2_for_immune_system.php Platzman Weinstock, C. (2013, November 4). The Latest Weapon in the Fight Against Cancer. In Huffington Post. Retrieved from http://www.huffingtonpost.com/2013/11/04/provenge-cancer- vaccine_n_4181851.html State of Cancer Immunotherapy. (2014, June). Fight Cancer With Immunotherapy. Retrieved Februatry 16, 2015 from http://www.fightcancerwithimmunotherapy.com/ImmunotherapyAndCancer/StateOfCancerImmunotherapy.aspx What Is Cancer Immunotherapy?. (2014, September 5). In American Cancer Society. Retrieved February 16, 2015 from http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-what-is-immunotherapy http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-what-is-immunotherapy What Is Immunotherapy?. (2013, March). In Cancer.Net. Retrieved February 16, 2015 from http://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and- vaccines/what-immunotherapy http://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and- vaccines/what-immunotherapy