BREAKING THROUGH 2014 Annual Report OUR MISSION: FROM CRI’S SAVE MORE LIVES WITH CANCER IMMUNOTHERAPY LEADERSHIP Established in 1953, the Cancer Research Institute (CRI) is the world’s only nonprofit his past year was one of many breakthroughs for the ever have at one time before. We launched a new patient organization dedicated exclusively to saving TCancer Research Institute (CRI). Science magazine website, TheAnswerToCancer.org, designed to educate cancer patients’ lives by fueling the development named cancer immunotherapy the “Breakthrough patients and caregivers about cancer immunotherapy. We of smarter, more effective treatments that of the Year,” catapulting the work that CRI does celebrated our second annual Cancer Immunotherapy mobilize our immune defenses against all forms into the spotlight. It was also the year that several Month, mobilizing individuals and companies across of cancer. CRI supports the most innovative immunotherapies pioneered by CRI scientists received the world to participate in our education and awareness research of young scientists, invests in clinical “Breakthrough Therapy” status from the FDA, paving the activities. And our Clinical Accelerator program is studies of encouraging new treatments, and way for important new drug approvals. In September of spearheading several important clinical trials that are unites the efforts of the field’s leaders worldwide. 2014, U.S. regulators approved Merck’s drug Keytruda® bringing lifesaving immunotherapies to patients faster. With this work, CRI is turning our own immune (pembrolizumab) for the treatment of melanoma, making system into a powerful weapon against cancer. it the first PD-1 checkpoint inhibitor to receive FDA None of this would be possible without the generous approval and the third immunotherapy to be approved in support of our donors, who sustain our work and make just the past four years. tangible our vision of a world free from the fear of cancer. On behalf of our staff, our scientists, and our patients, Institutionally, CRI had a breakthrough year, as well. We thank you for all that you do to help CRI pursue its devoted $22 million to our programs—more than we mission to conquer cancer within our lifetimes. 01 From CRI’s Leadership 16 Awards and Honors James P. Allison, Ph.D. Jill O’Donnell-Tormey, Ph.D. 02 Breaking Through 18 Fiscal Year 2014 Director, Scientific Advisory Council CEO and Director of Scientific Affairs 04 Postdoctoral Program Grants and Awards 06 Clinic and Laboratory 29 Donors and Supporters Integration Program 45 Financials 08 Clinical Accelerator 47 Stewards of the 10 Thought Leadership Organization 55 Giving to the John B. Fitzgibbons Paul C. Shiverick 12 Patient Education Co-Chairman of the Board Cancer Research Institute Co-Chairman of the Board 14 Public Awareness Kunle Odunsi, M.D., Ph.D., at Roswell Park Cancer Institute Member, CRI Scientific Advisory Council CANCER RESEARCH INSTITUTE 2014 ANNUAL REPORT 1 Dendritic cells (green) use their spiny tendrils to present antigens to T cells (red). Photo courtesy of Olivier Schwartz, Ph.D., Pasteur Institute BREAKING THROUGH or this year’s annual report, we chose the Ftheme “Breaking Through,” in recognition of the tremendous progress being made in the field of cancer immunotherapy. We at the Cancer Research Institute (CRI) know that the current state of optimism about immune-based treatments for cancer would not have been possible without the decades of research that came before. We also know that future advances will depend upon continued financial support of the entire research spectrum, from basic science, to translational research, to clinical trials. With its more than 60 years of funding research to understand the immune system and how it can be harnessed to conquer cancer, CRI is leading the way and ushering in a new era when patients, with all types of cancer, can be Cancer immunotherapy offers the treated and one day cured with immunotherapy. “greatest hope of transforming cancer treatment in our lifetimes. Jill O’Donnell-Tormey, Ph.D., CEO and Director of Scientific Affairs The Cancer Research Institute “has been very wise in putting the majority of its money into people who will develop new ideas. James Watson, Ph.D., co-discoverer of the 01 structure of DNA and CRI grantee 26 new grants BASICS AT THE BENCH Optimizing Therapeutics Numerous CRI postdoctoral fellows are conducting $4.3 CRI postdocs pursue research into improving the effectiveness of existing million awarded immunotherapies and understanding the mechanisms by tomorrow’s breakthroughs today which they work. From uncovering new cancer antigens that can be used in therapeutic vaccines, to developing new The CRI-IRVINGTON n medicine, the most important breakthroughs usually targets for genetically engineered T cells, to understanding POSTDOCTORAL FELLOWSHIP how checkpoint inhibitor antibodies work to stimulate the 03 PROGRAM, established Icome from research aimed at understanding fundamental immune response, CRI postdoctoral fellows are bringing in 1971, is CRI’s longest- biological mechanisms. CRI is currently supporting the basic research to bear on topics of great clinical importance. running continuous program. basic laboratory research of 90 postdoctoral fellows, with Fellowships provide up to the understanding that tomorrow’s cures will be built on the $164,500 over three years to solid foundation of today’s basic discoveries. Inflammation, Microbes, and Cancer support young immunologists Chronic inflammation is believed to promote the POSTDOCTORAL and cancer immunologists development of several types of cancer, including studying at top universities Immune Evasion colorectal, liver, bladder, and lung cancers. CRI postdoctoral fellows are pursuing research aimed at understanding around the world. As cancer begins to develop, our immune system tries to eliminate the link between inflammation and cancer progression, it. However, immune cells are often unable to prevent cancer including the role that bacteria and viruses may play in this 02 04 development because their activity is inhibited in several ways, process. By finding ways to combat chronic inflammation, including by checkpoints that “put the brakes” on the immune scientists may one day be able to control the development response, and by regulatory cells that tell the immune system to “stand of inflammation-induced cancer, or prevent it altogether. down.” Cancer cells then escape detection and destruction by the 01 Noah W. Palm, Ph.D., and immune system and grow into tumors. CRI postdoctoral fellows are Watch the Video Nicola Gagliani, Ph.D. For a complete list of all exploring how immune evasion occurs and how it can be overcome, 02 Matthew Gubin, Ph.D. Gut Responses: Inflammation, Microbes, and Cancer with the hope of improving the effectiveness of immunotherapies. 03 Stefani Spranger, Ph.D. 90 postdoctoral fellows, www.bit.ly/gut-responses 04 Chunyu Jin, Ph.D. go to page 19. CANCER RESEARCH INSTITUTE 2014 ANNUAL REPORT 5 I definitely believe that the work I’m doing “is going to benefit cancer patients. Ryan M. Teague, Ph.D., CLIP Investigator 12 new grants BETWEEN Pulling the Rug Out Beta-Blocker Therapy for When Cancer Starves the from Under Tumors Breast Cancer Immune System $2.4 BENCH & Ellen Puré, Ph.D. Ming Li, Ph.D. Jeffrey Rathmell, Ph.D. million awarded Genentech Investigator Memorial Sloan Kettering Wade F.B. Thompson Investigator University of Pennsylvania Cancer Center Duke University Medical Center School of Veterinary Medicine New York, NY Durham, NC The CLINIC AND BEDSIDE Philadelphia, PA LABORATORY INTEGRATION PROGRAM (CLIP) supports Most conventional cancer therapies Suppression of the immune system Researchers have known for a long scientists who are exploring Where other funding agencies fear directly target cancer cells. In recent by cancer cells is believed to play an time that cancer cells compete with clinically relevant questions years, researchers have learned that important role in cancer progression. normal cells for energy and nutrients. aimed at improving the to tread, CLIP creates a bridge the cells surrounding a tumor are just Ming Li, Ph.D., is studying the Jeffrey Rathmell, Ph.D., is working immunosuppressive pathway that is to understand how this competition effectiveness of cancer as important. Ellen Puré, Ph.D., is activated in tumor-associated immune suppresses the immune system’s immunotherapies. CLIP grants ome of the most exciting questions in tumor using genetically engineered immune cells to kill the cancer-supporting cells in breast cancer models. This ability to fight cancer. In a model provide up to $200,000 over immunology today are ones being pursued at the “stromal” cells surrounding tumors. pathway is also the target of beta of kidney cancer, he has found TRANSLATIONAL S two years. interface between basic and clinical research. Yet few Called chimeric antigen receptor blockers, which are used to treat high that cancer cells starve immune funding agencies focus on this translational research. (CAR) T cells, these engineered cells blood pressure and which have been cells of important nutrients such as CRI’s Clinic and Laboratory Integration Program (CLIP) contain a protein receptor that turns associated with increased survival glucose and amino acids, leaving T cells into cancer fighters. Dr. Puré among breast cancer patients. Dr. Li them unable to marshal an effective was launched in 2011 to serve this unmet need. Current has shown that these CAR T cells can is investigating whether beta blockers immune response and altering their CLIP scientists are pursuing novel therapeutic strategies inhibit the growth of lung tumors in target T cells to control breast tumor function. His work also suggests that informed by the cutting edge of both laboratory and mice. They are now exploring whether development, and is also working therapies designed to block immune clinical research. Their projects are bringing innovative this immunotherapy can enhance the to understand how this pathway checkpoints, such as anti-PD-1 regulates T cell responses to tumors, antibodies, may act in part by shifting For a complete list of all therapies for patients closer to reality.