Current Funded Grants by Kids Beating Cancer

University of North Carolina at Chapel Hill

$126,200 grant

Scott Elton, PhD Co-Principal Investigator, Pediatric Neurosurgery, University of North Carolina Hospital
Shawn Hingtgen, PhD Co-Principal Investigator UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill
Oleh Taratula, PhD Co-Principal Investigator, College of Pharmacy, Oregon State University
James Baumgartner, MD Co-Principal Investigator, Pediatric Neurosurgery

Stem Cell-delivered Particles for Hyperthermia Therapy to Treat Glioblastoma

Glioblastoma (GBM) is the most common primary brain tumor and one of the deadliest forms of cancer¹. Median survival is little more than 12 months and has not improved significantly in over three decades. We propose an exciting new approach to GBM therapy that could mean a big leap towards finding a cure: tumor-homing cell-based hyperthermia therapy. We propose an exciting new approach to GBM therapy that could mean a big leap towards finding a cure: tumor-homing cell-based hyperthermia therapy. We hypothesize that engineered metal-loaded iNSC/oscillating magnetic field hyperthermia therapy will achieve GBM-selective homing and therapeutic efficacy that will prevent GBM progression. Across three Aims, we will convert human skin tissues into next-generation tumor-homing neural stem cell drug carriers termed iNSCs. We will load the iNSCs with custom-developed metal nanoparticles and investigate the fate, migration, efficacy of this novel strategy in clinically-relevant preclinical models of GBM. Our rationale is that iNSC drug carriers derived from the patient’s own skin will avoid immune rejection, seek out residual tumor foci that chemotherapy and radiation cannot reach, and effectively eradicate the tumor once a magnetic field is applied to generate heat that will selectively and efficiently induce tumor kill. We propose to test this hypothesis, defining the efficacy of this novel treatment and develop strategies to support translation into human clinical trials. We will investigate particle loading, impacts on iNSC viability, homing, and GBM kill. We will modulate a variety of parameters to optimize the therapeutic strategy, focusing first on the iNSC carrier then on maximizing GBM kill. All testing will be done using our validated nanoparticles, unique ex vivo living tissue brain slice model, and novel surgical resection models of patient-derived CD133+ human GBM cells to maximize the clinical relevancy of our finding and understand the impact of the immune system on iNSC treatment durability. If successful, this transformative platform will advance the field of cell therapy, shift NSC therapy for GBM towards a personalized hyperthermia-based approach and develop a broadly applicable patient-specific cell therapy strategy that could shape the future of clinical GBM therapy.

Making cold tumors hot: Multi-faceted Immunostimulatory Therapy for Ewing Sarcoma (MITES)

Ewing sarcoma (ES), the second most common bone cancer in children, remains a significant challenge in pediatric oncology.  Survival rates for patients with recurrent or metastatic disease have not improved for decades, and no targeted treatments have succeeded for broad clinical use.  Immunotherapy has revolutionized cancer treatment in recent years, but it has been poorly explored in the context of ES.  Recent studies show that some ES patients exhibit high infiltration of cytotoxic immune cells, and that this is associated with greatly prolonged survival. Yet, the tumor-intrinsic factors that drive this favorable, “hot” immune phenotype spontaneously in some patients is a mystery. Children’ Hospital of Philadelphia’s research has identified such a factor, USP6, which has potent and pleiotropic immunostimulatory effects in jumpstarting the immune system, triggering infiltration of immune cells into the tumor, and stimulating their ability to kill the cancer cells.  Concordantly, high USP6 levels are associated with dramatically improved survival in ES patients. These findings will be exploited to develop a novel immunotherapeutic agent to prevent ES recurrence and improve survival.

Nathan Singh, MD, PhD, Principal Investigator
Assistant Professor of Medicine; Division of Oncology, Washington University School of Medicine in St. Louis

Defining the epigenetic and transcriptional signatures of chimeric antigen receptor T cell dysfunction

Chimeric antigen receptors (CARs) are engineered proteins that re-direct a patient’s immune system to target their cancer.  T cells, the “killers” of the immune system, that are engineered to express CARs have demonstrated unprecedented results in the treatment of pediatric acute lymphoblastic leukemia, with ~9/10 patients becoming disease-free after treatment.  Despite these exciting initial results, follow-up now shows that only half of patients treated will remain disease-free long-term.  These clinical failures often result from failed T cell activity against leukemia cells. Washington University School of Medicine has recently identified that prolonged interaction between CAR T cells and leukemia cells can lead to T cell failure, however the biology responsible for this remains unclear.  This research aims to identify the ways in which CARs promote T cell failure.  Understanding this process will reveal strategies to engineer CAR T cells that are resistant to failure, resulting in more durable responses.

University Of Cincinnati

Emerging Scientist $7,000 grant 

YOU can save the life of a child. Only 4% of national funding supports  pediatric cancer research. Only YOU can change the odds and save our kids! Donate today to our Research Fund and Save Children’s Lives