ASCO-SITC Clinical Immuno-Oncology Symposium


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Optimizing Immunotherapy in the Cold Prostate Cancer Microenvironment Ravi A. Madan, MD, and James L. Gulley, MD, PhD A lthough sipuleucel-T was approved by the U.S. Food and Drug Ad- ministration in 2010 based on an overall survival advantage, 1 prostate cancer ap- pears to have been left out of the subsequent immunothera- peutic revolution in medical oncology, which has largely been fueled by immune check- point inhibitors. 2 Two trials with ipilimumab in metastatic castration resistant prostate cancer (mCRPC), prior to and following chemothera- py, were negative for a survival advantage. 3,4 Similarly, multiple small studies with anti–PD-1 and anti–PD-L1 therapies have yielded modest results. 5 The National Cancer Institute (NCI) is currently exploring multiple strategies to enhance the effica- cy of immunotherapy in pros- tate cancer. These studies are not just important to the field, but could have implications across all tumor types, provid- ing a means to expand the sub- group of patients who respond to immune checkpoint inhibi- tors as monotherapy. One likely obstacle in gen- erating antitumor immune responses is that the immuno- logically "cold" prostate cancer microenvironment may be de- void of sufficient immune cells to make PD-1/PD-L1 inhibition a viable strategy. 6 Therapeutic cancer vaccines may be one op- tion to drive immune cells to the tumor microenvironment through systemic activation initially against a specific tumor antigen. Proof of concept for this study was demonstrated in a neoadjuvant study conducted with sipuleucel-T, which was given prior to radical prostatec- tomy. 7 There were increased im- mune cells relative to baseline biopsies noted at the periphery of the tumor when the prostate was resected, suggesting pe- ripheral activation of immune cells via sipuleucel-T indeed did drive immune cells to the tu- mor microenvironment. 7 Vaccines in Immunotherapy A trial underway at NCI is looking to exploit the thera- peutic potential of sipuleucel- T. In this trial (NCT02933255), patients will be treated with the therapeutic vaccine PROS- TVAC, a poxviral-based vaccine targeting prostate-specific anti- gen (PSA) in the neoadjuvant Dr. Malcolm K. Brenner to Discuss Advances and Challenges in Cellular Therapies During Keynote I nternationally renowned clinical scientist Malcolm K. Brenner, MD, PhD, will pro- vide an overview of recent advances in the development of cellular therapies for can- cer during his keynote lecture, "Cellular Therapy for Cancer," on January 27. He will also dis- cuss the scientific and practical challenges facing the field today and potential strategies for over- coming them. Dr. Brenner is the Fayez Saro- fim Distinguished Service Pro- fessor at Baylor College of Medi- cine and founding director of the Center for Cell and Gene Therapy at the Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital. Introducing Cellular Therapies Into Clinical Practice Dr. Brenner devoted the past 30 years of his career to translat- ing basic research in cellular therapies into clinical practice. His group pioneered the use of marrow stem cells as the target in the first human gene transfer study conducted outside of the National Institutes of Health 1 and was among the first to study the safety and feasibility of post-transplant immunization. His more recent research has shown that T cells can be genetically modified to convey antiviral and antitumor activity without compromising safety. 2,3 In an interview with the ASCO-SITC Clinical Immuno- Oncology Symposium Daily News, Dr. Brenner discussed his lat- est research interests in T-cell immunotherapy, as well as the challenges associated with de- veloping cellular therapies and making them accessible to pa- tients with malignancies. Using Oncolytic Viruses to Stimulate the Immune System "There are two ways to get T cells to work—either by their native receptors or through ar- tificial chimeric antigen receptors—and we've been interested, and have seen benefits, from both," Dr. Brenner said. "We would now like to combine the use of both types of receptors in a single cell type and find ways of optimizing that function by using external stimuli, such as oncolytic viruses that can recruit T cells through the native receptor, and allow them to cause damage to the tumor through the chimeric receptor." Dr. Brenner explained that the advantage of an oncolytic virus is its ability to secrete different proinflammatory cytokines and generate a host immune response, which can then evolve to fight tumor cells. "If we are going to treat human solid tumors, we can't just in- telligently design a therapy, because solid tumors are so heteroge- IrAEs in Patients With Melanoma E ric D. Whitman, MD, FACS, answers a question posed by an attendee at a Best of ASCO ® Meeting. Dr. Whitman is the medical di- rector of Atlantic Health System Cancer Care and the founding director of the Atlantic Mela- noma Center. Question: How do you manage the adverse events from immunotherapy treatments in patients with melanoma? Answer: The advent of the checkpoint inhibitor class of im- munotherapeutic agents, now U.S. Food and Drug Adminis- tration (FDA)-approved across an increasing swath of tumor indications, has given rise to an equally broad set of previous- ly uncommonly encountered treatment-related side effects. See Prostate Cancer Microenvironment, Page 3 Biomarkers of PD-1/PD-L1 Axis Inhibitor Response Rate 4 Immunotherapy Information for Patients 4 Symposium Essentials 4, 10, 12, 15 Immunotherapy as Treatment for T-Cell Lymphoma 6 Immunotherapy for Melanoma Brain Mets 7 Keynote Address Preview 8 SITC Educational Offerings 9 Immunotherapy in Sarcoma 12 Combining Immunotherapy With Radiotherapy 14 Advances in the Management of irAEs 15 Dr. Malcolm K. Brenner See Melanoma, Page 3 Clinical Corner INSIDE See Challenges in Cellular Therapies, Page 6 Attendee Tip of the Day Listen to the ASCO Daily News Podcast Series, where oncologists discuss the latest research and therapies in their areas of expertise. Download the ASCO Daily News podcasts to your iOS or Android device on iTunes or Google Play. ASCO-SITC Clinical Immuno-Oncology Symposium 2 0 1 8 daily news F R I DAY, JA N UA RY 2 6 • S A N F R A N C I S C O Visit for live Symposium coverage.

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