b'POWERING CURESThe generous support from the Pediatric Cancer Research Foundation has been pivotal in We are determined to fund research that propels scientific knowledge forward and advances new treatment breakthroughs. In 2023, we investedpropelling forward our dedicated research into rare pediatric cancers. This funding not only a total of $2,002,881 in research programs. Your support of novel science is helping to create new frontiers of understanding and treatment, asenhances our capacity to explore innovative treatments but also brings new hope to families these three examples illuminate. affected by these challenging conditions. We are deeply grateful for PCRFs commitment to ALEX HUANG, MD, PhD transforming the landscape of pediatric cancer research. ~ Dr. Rajkumar VenkatramaniProfessor of Pediatrics at Case Western Reserve University School of MedicineRAJKUMAR VENKATRAMANI,MD, MS, MBA, FAAPWhile working to develop new therapeuticAND ANDRAS HECZEY, MD options for pediatric sarcomas, Dr. Alex Huang,Texas Childrens Hospital/Baylor College of Medicinea professor of pediatrics at Case Western Reserve University School of Medicine, wasDr. Rajkumar Venkatramani is the director of the rare tumors program at Texas challenged to understand why certain patientsChildrens Hospital. He and his collaborator, Dr. Andras Heczey, set out to answer responded more positively to cryoablationan important question in their efforts to develop an effective immune therapy treatment than others. Dr. Huang wasfor children with malignant rhabdoid tumors (MRTs). Dr. Heczeys lab focuses perplexed by the results he received whileon understanding which genes are involved in a phenomenon called CAR T cell conducting tests on lab animals. The animalsexhaustionwhen CAR T cells are no longer able to recognize, kill and proliferate responded well to the procedure, in a mannerin response to tumor cells.that suggested the presence of STINGa DNA-detecting signaling moleculein theirWhile certain genes can help CAR T cells overcome exhaustion, it is unknown immune systems. The problem? The animalswhich genes perform this task most effectively. To solve this problem, they in question didnt have any STING in theirdeveloped a system called MOTOR to assess each of an estimated 3,000 genes in immune systems. That led Dr. Huang and hisCAR T cells using barcoded DNA technology. Preliminary results demonstrate team to ask if STING signaling doesnt comethat the MOTOR system works. Importantly, MOTOR also identified new master from the immune cells like always believed butregulators to prevent and to rescue CAR T cells from exhaustion. Dr Huang with a childhood leukemia survivor and one-time patient who is now a studentcould instead be caused by the tumor cells.The team is now repeating experiments to assess if the findings can be applied Two years of research proved that this is in fact the case. Published in The Journal for ImmunoTherapy of Cancer, the findings upended earlierto multiple tumor types. The top gene that can prevent CAR T cell exhaustion notions and produced an important finding that has significance for enhancing treatment efficacy.will be selected for further clinical development in children. The experiments are The Pediatric Cancer Research Foundation is pleased to have contributed funding to this and other research designed to support an Investigational New Drug application to the US FDA to being conducted by Dr. Huang. implement a Phase 1 clinical trial.We are proud to support this work through the Will Irwin Memorial Fund.Dr. Rajkumar Venkatramani and Dr. Andras HeczeySARAH RICHMAN, MD, PhD Childrens Hospital Los Angeles I am deeply grateful for the generous funding my group was awarded from the Dr. Sarah Richman, a physician-scientist in the Cancer and Blood Disease Institute atPediatric Cancer Research Foundation. These funds have allowed us to overcome Childrens Hospital Los Angeles, set out to explore the development of more effectivethe financial inertia to start a project that we are highly motivated to advance to a and less toxic approaches to chimeric antigen receptor (CAR) T cell therapy to treat patients with high-grade glioma. In this pilot study using mouse models, researchersclinical trial. By enabling my team and me to procure the necessary materials for the evaluated the impact on tumors of T cells that were not engineered (control preclinical experiments, PCRF has helped us produce data that led to securing a multi-T cells) compared to T cells that were engineered. Thirty (30) days after treatment,year foundation grant for this project. As a result, we attracted and hired a talented the control T cells had no effect on the tumors. However, the engineered CAR T cells eliminated more than 99% of the tumor cells and were both precise andPhD student with extensive cell engineering experience and successfully proposed a discriminating, having no observed effect on the control targeta promisingunique inter-campus, interdisciplinary training plan.sign of the therapys potential to impact diseased cells while leaving healthy cellsYour gift was truly the spark needed to launch this project in auntouched. These preliminary data have allowed Dr. Richman and her colleagues tomeaningful and exciting way.design a large-scale experiment that will enable them to better ascertain the timing of CAR T cell activity, plan the type of tumor modeling needed and estimate the number~ Dr. Sarah Richmanof mice required to yield statistically meaningful data.11'