Funded Research Projects
Year Awarded: 2022
Amount Awarded: $60,000
Institution: UCSF, Benjamin Huang, MD
Focus Area: Acute Myeloid Leukemia
Summary of Project: Acute myeloid leukemia (AML) remains a therapeutic challenge with high mortality rates despite intensive therapies. Furthermore, cure rates for pediatric AML have not significantly improved for nearly 30 years due a lack of effective biology-based therapies. While immunotherapies have yielded remarkable outcomes in B-cell acute lymphoblastic leukemia (B-ALL), identifying similar immunotherapy targets in AML remains a challenge due to similarities between AML and normal blood cells and early AML immunotherapy-based clinical trials have been disappointing to-date. To address the issue above, Dr. Huang’s team integrated large, advanced sequencing and protein datasets to identify potential targets expressed in pediatric AML, but not in normal bone marrow or other normal tissue types. Using this integrated approach, they identified a collection of new promising immunotherapy targets. Based on their promising preliminary data, they propose to validate the expression of these targets using cell surface proteomics, a powerful technology that identifies hundreds to thousands of cell surface targets simultaneously within a given leukemia cell population. Dr. Huang’s team will then use accurate models of AML to test whether using drugs that recognize these targets specifically will potently kill AML cells.
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Year Awarded: 2023
Amount Awarded: $66,000
Institution: Mayo Clinic of Jacksonville, Dr. Hong Qin, MD,PhD and Dr. Rocio K. Rivera-Valentin, MD, PhD.
Focus Area: Pediatric Brain Tumors
Summary of Project: Our project aims at using Chimeric Antigen Receptor (CAR) T cells specifically designed to recognize PDL1 and using this interaction to generate activated T cells that can recognize and kill cells that express this ligand. We have observed that DIPG and other high-grade glioma patient derived cell lines express high levels of PDL1 and co-culture with PDL1 targeted CAR-T can lead to T-Cell activation. We plan to further evaluate this CAR-T construct using in-vivo models with intracranial delivery of CAR-T cells and complete pre-clinical data to develop a Phase 1 clinical trial.
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Year Awarded: 2023
Amount Awarded: $100,000
Institution: Children’s Hospital of Philadelphia, Dr. Bagatell, Head of Neuroblastoma Research.
Focus Area: Neuroblastoma
Summary of Project: The COG Neuroblastoma Committee and the COG Foundation are currently developing a plan in conjunction with
Nationwide Children’s Hospital for a large-scale project that would include whole exome sequencing, RNA
sequencing, and methylation profiling on tumors from patients with more favorable neuroblastoma diagnoses who
nonetheless went on to progress with poor outcomes.
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Year Awarded: 2024
Amount Awarded: $50,000
Institution: UCSF, Benjamin Huang, MD
Focus Area: Acute Myeloid Leukemia
Summary of Project: Acute myeloid leukemia (AML) remains a therapeutic challenge with high mortality rates despite intensive therapies. Furthermore, cure rates for AML have not significantly improved for nearly 30 years due to a lack of effective biology based therapies. While immunotherapies have yielded remarkable outcomes in B-cell acute lymphoblastic leukemia (B-ALL), identifying similar immunotherapy targets in AML remains a challenge due to similarities between AML and normal blood cells. Therefore, we integrated large advanced sequencing and protein datasets to identify potential targets expressed in AML, but not in normal blood cells or other organs. Using this integrated approach, we identified a collection of new promising immunotherapy targets. Based on this high throughput analysis, we found that CSPG4 is among the leading targets that is more highly expressed in leukemias with KMT2A-rearrangements (compared to normal blood cells or other organs) and represents a promising therapeutic target for childhood AML. Therefore, we propose to engineer chimeric antigen receptor (CAR) T-cells to recognize CSPG4-positive leukemias and optimize the CAR design to potently and specifically kill AML cells in preclinical model systems. Our overall goal is to functionally validate CSPG4 as an immunotherapy target for childhood AML, and our studies will pave the way for clinical trials targeting CSPG4 and other candidate immunotherapy targets in children, adolescents, and young adults diagnosed with AML.
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Year Awarded: 2024
Amount Awarded: $75,000
Institution: Dr. Rachel Reu at Seattle Children’s and Dr. Sumit Gupta at The Hospital for Sick Children, Toronto
Focus Area: Acute Lymphoblastic Leukemia
Summary of Project: The goal of Dr. Reu and Dr. Gupta’s work is to identify predictors of response to blinatumomab through two specific aims.
Aim 1: Identify genetic variations in patients’ immune systems that predict response to blinatumomab
Blinatumomab is a two-part compound. One side binds to the leukemia cells, the other to the patient’s normal T cells. T cells are cells of the immune system that fight infections but can destroy harmful cells like cancer cells. Thus, a patient’s normal immune system is needed for blinatumomab to work and get rid of leukemic cells. It is likely that patients who relapse after blinatumomab have problems with their immune system and these problems make blinatumomab not work as well. The researchers will use modern day genetic testing to figure out what parts of a patient’s immune system may be tied blinatumomab response.
Aim 2: Identify leukemia-specific genetic markers of blinatumomab response and resistance.
