Grants Search Results

Pediatric Burkitt Lymphoma (BL) arises from errors during immune (B cell) development. Treatment failure is associated with dismal outcomes, and many pediatric BL survivors will suffer long-term toxicities from therapy, highlighting the need to explore opportunities to identify patients who may be cured with less intense therapies. Little is currently known about the biology of pediatric BL and clinical implications of specific mutations. Therefore, systematic analysis of tissue from children treated on clinical trials represents a unique opportunity to gain insights from valuable specimens to inform biologic risk-based chemotherapy and identify potential targeted therapeutic strategies. Dr. Allen will characterize intrinsic and acquired genetic factors that underlie pathogenesis and predict response to therapy in patients with pediatric BL who have completed treatment on COG clinical trials. This grant is funded by and named for Jack's Pack - We Still Have His Back, a St. Baldrick's Hero Fund. Jack Klein was a ten year old who loved life, laughing and monkeys. During his illness, his community of family and friends near and far rallied around him under the moniker "Jack's Pack". Their slogan was "We have Jack's Back". After Jack succumbed to Burkitt's Lymphoma, his "pack" focused their energy and efforts to funding a cure...just as Jack would have wanted.

Each year, approximately 1000 Americans aged 20 years or younger are diagnosed with acute myeloid leukemia (AML). Currently, even the most effective targeted drug BCL2 inhibitor-venetoclax (VEN) cannot eradicate all leukemia cells. The remaining cells cause disease recurrence and result in a very low overall survival rate for AML patients. In preliminary studies, Dr. Li found that targeting an enzyme called ADSS2 promotes pediatric AML cells sensitivity to VEN induced mitochondrial apoptosis, resulting in a synthetic lethality. This study will ask how ADSS2 preserves AML cells fitness and test the effectiveness of a first-in-class ADSS2 inhibitor combined with VEN or other BCL2 family protein MCL1 inhibitor in models of AML. If successful, this could lead to a clinical trial with potential impact for childhood AML patients.

Cancer cells compete with the body for food. Some cancer cells use fat to grow, spread, and hide in the brain. When cancer cells hide in the brain, it is hard for chemotherapy reach them due to the blood brain barrier, which allows cancers to come back when they come out of hiding. Dr. Wang and colleagues are investigating how childhood leukemia uses fat to survive in the brain and how drugs that starve leukemia of fat can kill leukemia cells hiding in the brain. The second year of this grant is generously supported by Rhys’ Pieces of the Cure, a Hero Fund created to honor Rhys Goldman and his journey with cancer. He was diagnosed with pre-B acute lymphoblastic leukemia just 2 weeks before his 6th birthday and endured treatment for three years. Rhys missed a lot of school and life during those years but since marking the end of treatment in July 2018, he has been enjoying swimming, singing in a boys’ choir, chess tournaments, playing with his dogs and going to school. Rhys’ Pieces for the Cure was created to ensure more research is funded for the treatment of pediatric cancer that is specifically focused on less toxic cures for kids.

Children with the brain tumor ependymoma have high relapse rates and poor long-term survival. Treatment options for ependymoma are limited and there is no known effective chemotherapy. Dr. Lindquist is working to make a new model of this tumor, to study how the tumor forms and grows, and to test new therapies in this model and patient-derived tumors. The ultimate goal is to identify new therapies that will extend the lives of children with ependymoma.

Ewing sarcoma (EwS) is a malignant cancer of bone and soft tissues that occurs mainly in children, adolescents and young adults. If the tumors spread, fewer than 1/3 will survive. For some pediatric cancers, recent progress has led to new treatments that use one's own immune system to target cancer cells. However, immunotherapy has not been successful for EwS because we don't know enough about how EwS tumor cells evade the immune system. The tumor microenvironment (TME) is an intricate ecosystem consists of cancer cells and the host's immune system. Dr. Kuo's project will focus on dissecting the TME of EwS, to understand how tumors develop. Using EwS tumors removed from pediatric patients during their cancer diagnosis and treatment, Dr. Kuo will use newly-developed techniques to map the TME and use a genetic model of EwS developed at CHLA to examine tumor/immune cell interactions in living tissue. The long-term goal of this work is to identify new treatment options for children with EwS. This grant is funded by and named for The Shohet Family Fund for Ewing Sarcoma Research. In his freshman year of college, Noah was diagnosed with Ewing sarcoma. He endured many months of chemotherapy and had limb salvage surgery. Able to return to school, Noah had no evidence of disease for 2½ years until April 2018 when routine scans revealed he had relapsed. He passed away in May 2021 at the age of 25. Noah and his family were always passionate about the need for curative treatments for diseases of the AYA population. The Shohet family intends to raise funds for this Hero Fund in Noah's memory to find cures for Ewing sarcoma and to carry on his legacy of possibilities and hope.

Osteosarcoma is the most common bone tumor in children yet the survival rate remains low, below 75%. Children who are born with or develop certain mutations or who have been exposed to radiation or chemotherapy are more likely to get this cancer. However, not enough is known about how osteosarcomas develop. To learn more, researchers must better understand how normal bone cells become osteosarcoma cells. Dr. Cantor and colleagues have previously seen that patients with this cancer have elevated serum levels of abnormal DNA sequences (repetitive element DNAs) that may affect how these cells behave. Dr. Cantor and colleagues are creating models that mimic the cancer formation process to define the factors that drive the production of these abnormal DNA sequences and the effects of such sequences on the osteosarcoma cell behavior. Through these studies, Dr. Cantor hopes to learn more about this previously unrecognized abnormality. Better understanding of this process may allow researchers to develop new therapeutic approaches for children with osteosarcoma.

The goal of this project is to engineer immune cells to target cancer, particularly a type of pediatric cancer called acute myeloid leukemia (AML). AML cells develop strategies to escape surveillance by the immune system. Despite current therapies, cancer cells are able to survive and progress. Natural killer (NK) cells play an important role in the immune response to cancer by recognizing and killing tumor cells. NK cell activity is regulated by activating and inhibitory receptors. Tumor cells express proteins that provide inhibitory signals to NK cells, blocking NK cell anti-tumor functions and allowing for tumor escape. Dr. Campbell and colleagues propose to tip the balance in favor of immune cell activation by knocking out a key NK cell inhibitory receptor, TIGIT. Dr. Campbell hypothesizes that eliminating NK cell TIGIT expression will remove inhibitory "brakes" on NK cell activation and enhance anti-tumor activity. The purpose of this study is to develop an effective cellular therapy for pediatric AML.

Acute Myeloid Leukemia (AML) is a blood cancer that sadly takes the lives of many children each year, and major efforts are being made to save these lives. One idea has been to teach the patient's body to fight off the AML like it would fight off an infection. This strategy alters the patient's immune system by making CAR-T cells, which are cells that fight cancer. CAR-T cells have been successful in curing patients with another similar type of blood cancer, but when it was tried in patients with AML, the approach was less successful. Dr. Anand's project is to understand why it didn't work as well so that further improvements that lead to cures for kids with AML can be made. This grant is generously supported by the JJ's Angels Hero Fund which honors the memory of Juliana LaMonica and her courageous battle with AML. Diagnosed at the age of two, Juliana underwent a bone marrow transplant but passed away shortly after turning three. Her sweet spirit and charismatic personality continue to inspire people to support the funding of pediatric cancer research through Team JJ’s Angels.

Burkitt lymphoma (BL) is the fastest growing, most aggressive pediatric tumor. In the 1960s, it was universally fatal. Over the past decades, clinical trials identified very high dose chemotherapy therapies as effective. Over 95% of children with BL in the US now survive. However, over 80% of cases of BL arise in children in sub-Saharan Africa (SSA) and other lower income regions where high dose chemotherapy is not currently feasible and in these settings BL is typically fatal. In the study, Dr. Allen builds on the observation that BL tumors from US and SSA are largely indistinguishable, but surprisingly tonsils from children in SSA and US have vastly different gene expression patterns. He therefore hypothesizes that the much higher rate of BL in SSA may not be due to intrinsic cancer cell factors, rather due to the nature of lymphoid tissues out of which the cancer cells grow. If Dr. Allen and colleagues can identify factors that lead to BL, they hope to create opportunities to prevent and treat BL in SSA. This grant is funded by Danilo Gallinari and the National Basketball Players Association.

The majority of children with newly diagnosed Burkitt lymphoma (BL) are cured. Unfortunately, the outcome is poor for patients whose disease returns (relapse). The relapse is caused by multiple reasons but mainly is due to drug resistance and suppression by the tumor surroundings. Novel therapeutic approaches are urgently needed. Natural killer (NK) cells can attack cancer cells. Dr. Cairo is developing immunotherapeutic agents to enhance the functions of NK cells to kill BL. Expanded NK cells will be modified by genetic techniques to specifically target CD20 and a special protein will be developed to bind to another surface protein CD19 on BL. A virus will be created to secrete IL21 to enhance NK persistence and function. If successful, the combinatorial therapies will become available to pediatric BL patients in the clinical setting and would offer a potentially more effective and less toxic therapeutic approach, ultimately leading to improved survival. This grant is funded by and named for Jack's Pack - We Still Have His Back, a St. Baldrick's Hero Fund. Jack Klein was a ten year old who loved life, laughing and monkeys. During his illness, his community of family and friends near and far rallied around him under the moniker "Jack's Pack". Their slogan was "We have Jack's Back". After Jack succumbed to Burkitt's Lymphoma, his "pack" focused their energy and efforts to funding a cure...just as Jack would have wanted.

Ewing sarcoma, an aggressive bone cancer that occurs in children and young adults, is caused by an abnormal chimeric protein (EWS-FLI1) that prevents cells from maturing into normal connective tissues through a process known as cell differentiation. How EWS-FLI1 acts to stop differentiation, however, remains an enigma. To solve this problem, Dr. Ludwig uses powerful gene editing tools to systematically turn the EWS-FLI1 protein up or down, then measures whether such changes allow cancer cells to behave more normally. The information gained from this research is expected to lead to new anti-cancer treatments for adolescents and young adults battling Ewing sarcoma. This grant is named for The Shohet Family Fund for Ewing Sarcoma Research. Noah was diagnosed with Ewing sarcoma in his freshman year in college. After limb salvage surgery and chemotherapy, he was able to return to school. Two years later, Noah relapsed and sadly passed away. This Hero Fund honors his courageous fight and hopes to raise funds for Ewing sarcoma research.

There has been little recent progress in treating Ewing sarcoma, a pediatric tumor involving bone. Dr. Stegmaier and colleagues have used a technology called CRISPR to identify urgently needed, new therapeutic targets for this disease. They prioritized a class of targets which are expressed in immature but not mature tissues. These proteins are often abnormally re-expressed in cancers such as Ewing sarcoma. Thus, drugs targeting these proteins would be expected to have minimal toxicity. The Stegmaier lab identified the target IGF2BP1 as a top selective gene dependency in Ewing sarcoma; deletion of IGF2BP1 was more deleterious to Ewing sarcoma than all other cancer types screened. Importantly, IGF2BP1 is not expressed in most normal human cells. Dr. Stegmaier will validate IGF2BP1 as a therapeutic target in Ewing and will determine the mechanisms by which Ewing sarcoma cells rely on IGF2BP1 for growth. With IGF2BP1 chemical inhibitors in development, this project has exciting translational potential for patients with Ewing sarcoma. This grant is funded by and named for The Ben Brandenburg Fund for Ewing Sarcoma Research. Ben passed away at the age of 15. He is remembered for his quick wit, indomitable spirit and bravery. This fund is his lasting legacy and ensures that research is funded so fewer children will have to suffer from Ewing Sarcoma.

Limited progress has been made over the last 30 years against kid brain tumors, especially those in the thalamus and the pons (Diffuse Intrinsic Pontine Glioma, DIPG), a specific location in the brain. Radiotherapy (RT) is the only treatment available that can prolong the life of children with the most aggressive form of brain tumors. Recently, RT is recognized to activate the immune system against multiple tumors. However irradiated kid brain cancers always regrow which suggest that RT is not activating immunity against these tumors. Understanding why this phenomenon is happening is critical to develop strategies that will exploit the immune stimulation from RT to control and cure brain cancer. The activation of cancer-associated fibroblasts (CAFs) by RT can be responsible for treatment resistance and the lack of immune stimulation of kids brain cancers. Dr. Vanpouille-Box's initial results show that stopping the immunosuppression of CAFs with a fibroblast activating protein alpha (FAP) blocker re-activates the immune system against irradiated pediatric brain tumors. Thus, blocking CAF emerges as a novel approach to prevent brain cancer regrow and to activate immunity in irradiated brain cancer. She proposes to: 1) Define the role of CAF in mice models of pediatric brain cancer 2) Determine the efficacy of CAF and EGFR blockade in irradiated pediatric brain cancer. Dr. Vanpouille-Box and colleagues hope to find that: - CAF stop the immune stimulation of irradiated pediatric brain tumors - blocking CAF immunosuppression works well to reactivate immunity against irradiated brain cancer, especially on the context of epidermal growth factor receptor therapy. This grant is named for the Pray for Dominic Hero Fund. The fund was established in honor of Dominic Liples who lived with joy. He is remembered for compassion and determination while he faced his own difficult battle with a rare and aggressive brain cancer. The Pray for Dominic fund carries on Dominic's legacy of joy and hope by funding research for high-grade gliomas.

Based on the progress to date, Dr. Rahnama was awarded a new grant in 2024 to fund an additional year of this Fellow grant. Acute Myeloid Leukemia (AML) is a blood cancer that affects children. While there have been important advances in treatment and care of pediatric patients with AML, 20-40% relapse and have poor outcomes. Novel therapies are urgently needed to combat this disease. One treatment modality under investigation involves manipulation of the body's immune system by reprogramming immune cells with inherent anti-leukemia properties to specifically target AML cancer cells. Dr. Rahnama is focused on the study of natural killer (NK) cells as immune cells of interest. NK cells can be engineered to express Chimeric Antigen Receptors (CARs) that recognize specific proteins on leukemia cells in order to attack and kill them. The site where the CAR-modified NK cell and the target leukemia cell come together is known as the immunological synapse (IS). The IS is highly organized and plays a key role in activating the NK cell. Dr. Rahnama aims to better understand the interaction between CAR-modified NK cells and target leukemia cells by studying the biology of the IS as related to how tightly the two cells interact. Her goal is to improve CAR-NK cell design for ultimate use as pediatric AML treatment. This grant was awarded at Johns Hopkins University School of Medicine and transferred to the University of California, San Francisco. This grant is funded by and named for the Aiden's Army Fund. When he was 8 years old, Aiden Binkley was diagnosed with Stage IV rhabdomyosarcoma. He had a huge tumor in his pelvis and the cancer had metastasized to his lungs. But this bright, funny and courageous boy believed he got cancer so he could grow up to find a cure for it. Aiden’s story has inspired so many people and his vision to cure cancer is being carried on by Aiden’s Army through the funding of research. They will march until there is a cure!

Based on the progress to date, Dr. Young was awarded a new grant in 2024 to fund an additional year of this Fellow grant. Osteosarcoma is a bone tumor that usually occurs in children and young adults and can be deadly especially when the tumor spreads to other body parts. The treatment strategy for this disease has not seen significant improvement in over 30 years, and there is no specific treatment for tumors that have spread throughout the body. In this project, the major goal is to identify factors that control the spread of osteosarcoma in order to develop new therapies to extend the lives of patients. Currently, Dr. Young is investigating whether osteosarcoma cells block the activation of one part of the patient's immune system, protecting the cancer cells from an immune attack and allowing them to spread throughout the body. This work has the potential to uncover new treatments to harness the immune system to fight this devastating disease. This grant is named for the Team Jackson Hero Fund. The fund was established in honor Jackson Schmitt who died six days after his diagnosis with osteosarcoma from a stroke. Jackson’s story was told worldwide and his legacy lives on through funding life-saving osteosarcoma research.

Brain and spine tumors are the leading cause of cancer-related death in children and adolescents. While cure can sometimes be achieved with conventional chemotherapy, surgery, and/or radiation, prognosis is dismal for patients whose aggressive brain/spine tumors progress despite these treatments. There is a critical need to develop new effective, well-tolerated therapies for children, adolescents, and young adults with refractory high-grade brain/spine tumors. Lutathera is a targeted radiotherapy which binds to tumor cells that express somatostatin receptors, causing tumor cell death through localized release of radiation, with minimal side effects. Many pediatric and young adult high-grade brain/spine tumors express somatostatin receptors, making them ideal targets for this therapy. Dr. Lazow is conducting a clinical trial to assess the safety and effectiveness of Lutathera in children and young adults with recurrent high-grade brain/spine tumors. Within this trial, she will also 1) evaluate how somatostatin receptor expression varies across different brain/spine tumors and determine clinical, imaging, pathology, and genetic characteristics which correlate with that expression, 2) identify imaging and molecular biomarkers predictive of response to Lutathera and/or disease recurrence, and 3) perform radiation dosimetry to establish optimal dosing of Lutathera in children and young adults, ensuring adequate tumor penetration while minimizing toxicity. If Lutathera proves safe and effective in treating children and young adults with refractory brain tumors, further studies will be planned to expand to a larger patient population and eventually incorporate Lutathera into upfront treatment backbones for these aggressive diseases. This grant is funded by and named for the Miracles for Michael Fund, a St. Baldrick's Hero Fund created in memory of Michael Orbany who was diagnosed with medulloblastoma when he was 6 years old. After completing initial treatment, his cancer relapsed within a year and he passed away at the age of nine. Michael had unwavering faith and perseverance, wanting most of all to make others happy. This fund honors his tremendous strength to never ever give up.

High-risk medulloblastoma is a devastating childhood brain cancer that results in death in nearly 50% of patients. To improve future treatments for this disease, Dr. Prensner is studying a category of newly-discovered "dark proteins", which have been excluded from prior work due to their small size and unconventional locations in the human genome. He has found that a group of these dark proteins are critical for medulloblastoma cells to survive. This research will reveal how these dark proteins may point toward new approaches to treat medulloblastoma, which may be critical to define the next generation of anti-cancer therapies in this disease. This grant was awarded at Dana Farber Cancer Institute and transferred to the University of Michigan.

Dr. Sykes is developing new therapies for childhood leukemia and lymphoma. Specifically, he is looking at a type of leukemia that develops from abnormal T-cells and is named acute lymphoblastic leukemia (T-ALL). T ALL is a particularly deadly disease if it does not respond to therapy (refractory) or if it responds initially and then comes back (relapsed). When a normal T cell becomes a leukemia cell, it develops certain advantages and certain disadvantages. Therefore, one way to kill a leukemia cell is to identify these disadvantages and to exploit those using specific drugs. This research focuses on how leukemia cells make DNA and RNA building blocks called nucleotides. An enzyme called DHODH is essential to the process of making nucleotides within the leukemia cell. Drugs that inhibit this enzyme rapidly kill the leukemia cells and spare the life of normal cells. Researchers call this approach 'nucleotide starvation' because it starves the leukemia cells of these DNA and RNA building blocks. Normal cells have back-up systems to deal with periods of nucleotide starvation. Dr. Sykes believes that leukemia cells have lost these back-up systems and that is why they are so sensitive to starvation. So far his research has shown that this nucleotide starvation approach works extremely well in leukemia cells outside of the body and in leukemia cells in laboratory mouse leukemia models. The fact that many DHODH inhibitor drugs are already available and have already been tested in humans suggests that clinical trials are feasible and could begin in a timely manner. Dr. Sykes hopes that DHODH inhibitor therapy will be effective treatment for children with T ALL, especially those children who have run out of other good treatment options.

There is no nice way to tell someone they've got a brain tumor, and with a child it’s unimaginable. In fact, brain tumors are the leading cause of solid tumor cancer death in children. Proteasome inhibitors are a recently discovered drug class that is effective in many types of cancer and have reduced side effects to normal cells. Dr. Almaliti aims to develop novel potent and selective proteasome inhibitors that will specifically kill brain cancer in children. This innovative approach should result in the discovery of new clinical leads for treating brain cancers in children. This grant is funded by and named for Luke's Army Pediatric Cancer Research Fund. This Hero Fund was created in memory of Luke Ungerer who brought smiles and sunshine wherever he went with plenty to share with everyone. He battled a brain tumor with a positive spirit and inspired others with his courage in his short life. This fund intends to carry on Luke’s legacy of positivity with the hope that it will ripple across many lives for many years to come.

Cancer research allows scientists to modify specific immune cells to recognize and kill cancer. One type of immune cell is called the cytotoxic killer T cell. This T cell has a receptor (TCR) that is used to recognize a structure on the cancer cell's surface called a peptide-major histocompatibility molecules complex I (pMHC I). pMHC I complexes are diverse and are rarely shared amongst patients. This diversity prevents the use of a classic TCR across multiple patients to avoid tissue injury that known as graft versus host disease (GVHD). To bypass these limitations, Dr. Elsabbagh propose to develop T cells expressing a TCR that can target a protein called CD1d. Unlike MHC I, CD1d is not diverse and is well expressed on various childhood cancers including acute myeloid leukemia (AML), which has been known for high rates of treatment-related toxicity and disease recurrence. These modified cells will be pre-made and used universally in any AML or other children’s cancers that expresses CD1d. Dr. Elsabbagh and team will also attach a recent discovered enhancing protein called MyD88 to the created receptor to enhance their anticancer activity. They expect these modified T cells will be able to recognize and kill children AML cells.