Pediatric Cancer Research Foundation

The Pediatric Cancer Translational Research Program focuses on four areas of research: 1) Stem cell transplantation and gene therapy for leukemia and lymphoma – Drs. Satiro de Oliveira/Ted Moore/Don Kohn/Gay Crooks, 2) The Pediatric Sarcoma Translational Research Program: Spanning the gap from bench to bedside – Dr. Noah Federman, 3) Dendritic Cell Vaccination for Pediatric High-Grade Glioma Patients – Dr. Tom Davidson, 4) Next generation sequencing and pediatric cancer predisposition – Dr. Vivian Chang. Members of the Pediatric Hematology/Oncology Division are members of COG, PBMTC, SARC, PPNOC, NYMC consortium among others.

Program Title: Targeted Inhibition of CREB for the Treatment of Pediatric Acute Leukemias The overall survival of pediatric patients with acute myeloid leukemia (AML) is 50% and less than 30% with relapsed acute lymphoblastic leukemia (ALL). CREB (cAMP Response Element Binding Protein) is a protein that is overproduced in leukemia cells from patients in AML. CREB increases the growth and survival of immature blood cells resulting in AML. In addition, overexpression of the CREB protein in AML patients was associated with an increased risk of relapse and decrease in survival. Knocking down CREB in AML cells resulted in cell death but had no long-term effects on normal blood stem cells. Therefore, we propose that CREB and its downsteam pathways may provide an alternative approach to treat acute leukemia. We developed a small molecule compound that blocks the interaction of CREB and its binding partner CBP (CREB Binding Protein). Our hope is that CREB inhibitors will lead to discovery of a new class of drugs that will be used to treat acute leukemia.   The quick brown fox jumps over the lazy dog.

Program title: Development of Tunable ON-OFF CAR T Cells for Safe and Durable Tumor Control Clinical trials conducted by our Ben Towne Center for Childhood Cancer Research (BTCCCR) at the Seattle Children's Hospital have reported 94% remission rates in patients with relapsed or refractory leukemia using T cells engineered to recognize and "kill" tumor cells based on specific cell surface proteins. Referred to as chimeric antigen receptor (CAR) T cell therapy, this strategy is also being tested against solid tumors (such as brain tumors and neuroblastoma) in ongoing FDA-approved clinical trials at the Seattle Children's Hospital. However, solid tumors pose formidable challenges to CAR T cell therapy - of note is the loss of T cell function inside solid tumors. It is believed that with repetitive attacks against tumors, T cells slowly enter a state of "exhaustion" or dysfunction wherein they shutdown their anti-tumor functions. This state of inaction is reinforced through negative signals from tumor cells, which further suppress their metabolic capacity for mounting an anti-tumor attack.

The PCRF Laboratory Research Program at MFCH at NYMC is focused on fiveoverarching areas of research/hypotheses. These state of the art research initiatives include: 1) cancer genetics and treatment of childhood and adolescent hematological malignancies; 2) genetically re-engineering immune cells to enhance targeted adoptive cellular cancer immunotherapy; 3) tumor immunology and identifying targets for humoral targeted immunotherapy; 4) stem cell biology, cancer stem cells, and regenerative therapy; and 5) translational therapeutic consortiums for childhood and adolescent cancer therapy.