Grants Search Results

Acute myeloid leukemia (AML) is the second most common type of leukemia in children. Despite treatment advancements, over 30% of children with AML cannot be cured. In AML cell populations, the leukemia stem cells (LSCs) make up a small part of the total, but are specially important: they provide a steady supply of new AML cells and are unfortunately very resistant to killing with drugs. Dr. Sui and colleagues believe that if they are able to kill the LSCs, they could cure patients with AML. Dr. Su has found that an enzyme called METTL1 is important in allowing LSCs to safely stay anchored in the bone marrow and identified a drug that inhibits METTL1 and eliminates LSCs. Dr. Su's study explores why METTL1 is important for LSCs and investigates how Dr. Su and team could best use their in-house developed METTL1 inhibitor to treat childhood AML using model systems. If successful, this research could pave the way for a clinical trial, offering hope for improved outcomes for childhood AML patients. This grant is generously supported by Double Deckers Destroy AML, a St. Baldrick's Hero Fund. Joel and Seth were not only identical twins but best friends. In an ironic twist of fate, both boys were diagnosed with Acute Myeloid Leukemia just three months apart. With the overlapping diagnoses and treatments, the family was separated for months at a time and looked forward to days when they could be together at home. Joel and Seth both received bone marrow transplants and endured complications from the procedures. Sadly, both boys relapsed. Surrounded by their loving family, Joel died in November 2017 at the age of three, followed by Seth in May, 2019 when he was four years old. The twins were named as 2020 Ambassadors for St. Baldrick's so their story can continue to inspire many. The Double Deckers Destroy AML Hero Fund was established because the Decker family strongly believes more research is needed for AML, especially when the disease has relapsed. They want to support research so other families won’t have to say goodbye too soon.

Allogeneic cell therapy is a new approach to cancer treatment that harnesses living cells from healthy donors to fight tumors. To do so, immune cells are isolated from blood and incubated outside the body to expand subsets capable of killing cancer. Dr. Jonus and colleagues have shown that gamma delta (gd) T cells expanded from healthy adults help to eradicate neuroblastoma grown in models. Based on this,Dr. Jonus and team are performing a first-in-child clinical trial of gd T cells for patients with neuroblastoma. Going forward, Dr. Jonus's findings show an opportunity to make gd T cell therapy more effective by expanding a new type of gd T cell, Vd1, with unique properties that should improve both the cell therapy's fitness and its ability to infiltrate into solid tumors. In parallel for a potent second-generation therapy, Dr. Jonus will engineer Vd1 gd T cells to 1) express receptors that help them better recognize neuroblastoma and 2) evade immune recognition so that the therapy is not killed after being infused into a patient. The first year of this grant is funded by and named for the Oliver Wells Fund for Neuroblastoma, a St. Baldrick's Hero Fund. From the moment he was born, Ollie was the center of the Wells family with a contagious smile and a sparkle in his eyes. As the youngest child, it was devastating when they learned the 15 year old toddler had cancer. Oliver was diagnosed with high risk neuroblastoma and spent the next 13 months bravely enduring chemotherapy and radiation, more than a dozen surgeries and a bone marrow transplant. But Ollie persevered and smiled through it all. It was an unfair fight from the beginning and in July 2018, Ollie passed away. The Oliver Wells Fund for Neuroblastoma was established in his memory to raise funds to find cures and give hope to other kids facing the same fight. In this way, the Wells family intends to share Oliver’s joy for life and use his story to help find a cure.

Medulloblastoma (MB) is an aggressive childhood brain cancer that is fatal in 40% of patients. MB shows abnormal activation of growth pathways in tumor cells which help them to grow. Dr. Ganesan's studies show that there are T cells (immune cells) within MB and they have potential to kill tumor cells. However, immunotherapy that boosts the activity of these T cells have not been successful and it is not known why. The goal of this project is to understand why immunotherapy has not worked in MB and whether immunosuppressive myeloid cells contribute to this restraint. Dr. Ganesan and colleagues will also study if combined treatment that inhibits the growth pathways (targeted therapy) and stimulates the T cells/immune system (immunotherapy) may together lead to greater tumor killing in MB mouse models. To test if combined therapy would work in humans, Dr. Ganesan will coculture a 3D version of patient’s brain tumor with their own T cells expanded from their tumor. If effective, these studies may lead to new treatments for MB.

The ultimate goal of this project is to define the safest, most effective therapies for children and young adults with Langerhans cell histiocytosis (LCH), which aligns with St. Baldrick's mission to find cures for childhood cancers and give survivors long and healthy lives. LCH is a blood cancer most common in children that creates destructive inflammatory lesions that can be fatal. LCH is caused by mutations activating the MAPK growth pathway in developing blood cells. Current front-line therapy fails to cure over 50% of patients with disseminated disease, and safe and effective options for subsequent therapy is not known. High-dose chemotherapy can be effective, but is toxic. MAPK inhibitor therapy alone does not appear to be durable based on early trials. Dr. Allen and colleagues hypothesize that MAPK inhibition will make cells more sensitive to chemotherapy. Dr. Allen will therefore test safety and efficacy of a new approach of combining chemotherapy with targeted MAPK inhibitor therapy.

Despite remarkable improvements in treatment for children with some types of cancer, pediatric brain tumors remain an area that desperately require more effective and low toxic therapy solutions. Dr. Jun Qi has formed a multi-disciplinary team to identify novel targets for pediatric brain tumors and develop new strategies to suppress the targets for patient treatment. Using a chemical strategy, Dr. Qi and his team aim to disrupt the functions of these targets to effectively inhibit brain tumor cell growth and block tumor progression in the models that resemble the real disease. The study focuses on improving on-target effect and, more importantly, on getting these potential drug candidates into the brain. The proposed study will translate from bench to bedside for patient care and result in a novel therapeutic strategy with significant improvements in survival and reduced morbidity for pediatric brain tumor patients to fulfill the mission of St. Baldrick’s Foundation.

The study of genetic disease of cancer predisposition has served as a model for understanding cancer in general. Fanconi anemia is a rare genetic disease of failed blood production and cancer proneness, including leukemia and head and neck cancer. The genes and encoded proteins participate in DNA repair. However, an examination of cancer databases of DNA sequence shows that Fanconi genes are mutated in up to 30% of all head and neck cancers in non-Fanconi patients. Dr. Kupfer and colleagues have studied one particular mutation that resides in the Fanconi FANCD2 gene that interrupts its protein binding to another important gene BLM, which also participates in DNA repair. This proposal will seek to study the normal function of the FANCD2-BLM interaction in the cell and the consequences of its disruption. Dr. Kupfer also seeks to identify ways disruption of the normal pathway will render cancers vulnerable to molecular targeting to improve therapeutics.

Cancer patients take life-saving drugs that, unfortunately, can result in peripheral nerve damage. For example, many patients receiving cisplatin experience permanent hearing loss. There is one therapy that has been approved to mitigate cisplatin-induced hearing loss, however, the reduction in hearing loss is modest (< 30%) and this mitigating treatment is associated with poorer overall survival rates due to inhibition of cisplatin's cancer-fighting properties. Thus, it is approved for low-risk pediatric patients only. To develop a better alternative, Dr. Rutherford and colleagues are testing novel compounds they have developed at Washington University, which have shown to protect the ear from noise trauma. With hearing tests and with anatomical measurements of the cochlea, Dr. Rutherford will attempt to prevent hearing loss following cisplatin treatment in models. After this innovative project proves successful, subsequent model studies will determine if Dr. Rutherford's therapy inhibits cisplatin's cancer-fighting role.

Brain tumors are the leading cause of cancer related death in children. The outcomes for high-grade gliomas in children are dismal. Chimeric antigen receptor (CAR) T cells are genetically engineered cells programmed to target cancer cells with high precision. The application of CAR T cells in brain tumors in children is still limited compared to leukemia. One challenge is that CAR T cells need multiple hits to kill brain tumor cells compared with leukemic cells, where a single hit is sufficient. Dr. Abu Arja and team discovered a subset of CAR T cells that are more potent and can more proficiently kill brain cancer cells by increasing their lethality, making a second hit unnecessary. In this project, Dr. Abu Arja is studying the cellular program of this unique subset of potent killer CAR T cells to better understand why they are superior killers. Dr. Abu Arja plans to use these findings to genetically engineer new enhanced CAR T cells to eliminate tumors in children with brain cancers. The first year of this grant is funded by and named for the Be Brooks Brave Fund. Despite his diagnosis at age 5 with inoperable brain and spinal tumors, Brooks taught so many people what life is truly about--love. He was BRAVE beyond his years with an inspiring “faith over fear” attitude. This Hero Fund hopes to raise money for high-grade glioma research so no other family will hear the words, “there is no cure”.

Neuroblastoma is a devastating pediatric cancer, with only 50% survival in aggressive "high-risk" disease. Survivors are burdened with life-long side effects from chemotherapy and radiation. Newer therapies, such as cancer vaccines, provide an opportunity to mobilize a patient's own immune system to find and destroy cancer cells. Identifying the unique genetic signature of an individual patient's tumor allows scientists to formulate a personalized vaccine to stimulate the immune system to recognize tumor-specific mutations, called "neoantigens". Dr. Spear has developed a new tool to identify these unique genetic signatures (neoantigens) and test the effectiveness of the neoantigen vaccine in modes. These findings will lay the groundwork to develop a clinical trial using personalized vaccines for high-risk neuroblastoma and other pediatric cancers. This grant is funded by and named for the Arden Quinn Bucher Memorial Fund, a St. Baldrick's Hero Fund. Arden’s intelligence, empathy, and dynamic personality charmed everyone and is now her legacy. Before her neuroblastoma diagnosis on October 11, 2007 at age two, she happily played with boundless energy and imagination. Even throughout her difficult months of treatment, Arden bravely managed to keep smiling and learning. This fund supports St. Baldrick’s mission: funding the most promising research, wherever it takes place to provide kids fighting cancers less toxic, more effective treatments allowing them to live longer, healthier lives.

Leukemia and lymphoma are blood cancers that are a major cause of death in children. Many of these cancers are curable with chemotherapy, but in some people the cancer comes back and is harder to cure. A new treatment called CAR-T cells involves genetic engineering of a cancer patient's own immune system cells to fight cancer, and can cure many people. However, this treatment still does not work well enough in about half the people who get it. Dr. Pauerstein proposes improving the sensitivity of CAR-T cells to cancer using engineered cell adhesion molecules, a type of molecular glue between two cells. CAR-T cells do not attach to cancer cells as strongly as normal T cells do, and this limits their ability to find and kill cancer cells. An engineered adhesion will be used in combination with CARs to improve the ability of CAR-T cells to kill cancer. Dr. Pauerstein and team will also study how changes in cell adhesion affect how CAR-T cells kill cancer. This work should improve cell-based treatments for blood cancers.

Hepatoblastoma is the most common liver tumor diagnosed in early childhood, and new therapies are urgently needed to improve survival and reduce treatment related morbidity. Immunotherapy is a type of cancer treatment that harnesses the body's own immune system to target and attack cancer cells. While some immunotherapies have been very successful against certain tumor types in adult patients, they have been largely unsuccessful in treating pediatric tumors. This demonstrates how little we know about how the pediatric immune system responds to tumors. Using samples and models of hepatoblastoma, Dr. Cabric's research aims to identify the key immune cells involved in recognizing and responding to hepatoblastoma. Identifying the key immune cells involved in tumor immunity, and mechanisms that allow tumors to escape detection and deletion by the immune system, will allow us to find novel targets for future immunotherapies that work in children. This grant is funded by Allied World, a global provider of insurance and reinsurance solutions.

Ewing sarcoma (EwS), the 2nd most common childhood bone sarcoma, is an aggressive tumour that primarily affects children, adolescents, and young adults. When EwS tumor cells spread to other parts of the body, known as metastasis, survival is drastically diminished to only 15-20%, which has not changed for decades. Immunotherapy empowers a patient’s own immune system to attack cancer, which has tremendous promise as an alternative to chemotherapies that are often toxic, especially to a growing child. Dr. Sorensen and his team recently identified a protein that is highly expressed on the surface of EwS cells, while showing only minimal to absent expression in normal tissues, nominating IL1RAP as a very promising therapeutic target. With their collaborators at the University of Pittsburgh, they have identified specific antibodies binding to IL1RAP and have engineered these antibodies to be conjugated to a drug that kills EwS cells potently. In this project, they will perform the extensive validation of these compounds to enable the design of early clinical trials for the treatment of EwS. This Better Ewing Sarcoma Therapies (BEST) grant is supported by a unique partnership of funders through the St. Baldrick’s Foundation: D-Feet Cancer, The Faris Foundation, The Shohet Family Fund for Ewing Sarcoma Research, an anonymous donor, and the family and friends of Martha Riedel.

Chimeric Antigen Receptor (CAR)-T cells have been clinically effective in patients with leukemias and lymphomas. Dr. Venkataraman’s goal is to bring similar success in treating a fatal brain tumor in children called DIPG (Diffuse Intrinsic Pontine Glioma). A major obstacle in treating brain tumors with CAR-T cell therapy is a lack of antigens which are tumor specific, or which are absent on normal vital tissues that can lead to off-target toxicities. To overcome this risk, Dr. Venkataraman and colleagues have successfully generated and tested the functionality of a novel “logic-gated” CAR-T cells targeting two distinct antigens, CD99 AND B7H3 that are highly expressed on DIPG but present singly on certain normal cells. This gated “AND” CAR-Ts will have full-activation against DIPG cells having both the antigens while sparing the single antigen expressing normal cells and will now investigate the safety, preclinical efficacy of these CAR-T cells against DIPG and evaluate its translational relevance to DIPG patients.

Children, adolescents and young adults with recurrent or refractory Osteosarcoma have a very poor prognosis, with a dismal 6mo overall survival of less than 5%. Presumably, this poor prognosis is in large part secondary to the development of resistance to chemotherapy and radiation. More recent studies employing therapies that release and activate the patients’ immune cells, called T-cells, and even targeted T-cells have not improved this poor prognosis. Dr. Cairo proposes to investigate novel and innovative methods of combinatorial immunotherapy to circumvent known mechanisms of resistance. Together with colleagues, he proposes to investigate at the bench (in the laboratory) and in models with osteosarcoma alternative methods of combination immunotherapy including natural killer cells (NK) that we have been engineered in the laboratory to also circumvent mechanisms of resistance and to additionally express a single or dual target that are present on the osteosarcoma cells. They further plan to investigate the efficacy of adding other immunotherapies to enhance the function and persistence of these targeted NK cells with antibodies, and two different NK activating cytokines. They will also investigate the optimal combination of this immunotherapy in children, adolescents and young adults with recurrent or refractory osteosarcoma to determine the safety and efficacy of this approach. Finally, Dr. Cario and team will determine what are the genetic and immune mechanisms of resistance after these novel combinatorial immunotherapy approaches utilizing state-of-the-art laboratory techniques. The goal of this grant is to develop novel combinatorial immunotherapy that will significantly increase the overall survival in children and adolescents with poor risk osteosarcoma. To make a significant impact for kids fighting osteosarcoma, five funders have banded together with St. Baldrick’s to support this grant – The Helping Osteosarcoma Patients Everywhere (HOPE) Super grant supported by Battle Osteosarcoma, the Faris Foundation, the Zach Sobiech Osteosarcoma Fund of Children’s Cancer Research Fund, the Children’s Cancer Fund NY (supporting the Maria Fareri Children’s Hospital and New York Medical College) and Nationwide Children’s Hospital.

CAR-T cell immunotherapies, treatments that use T cells constructed to recognize tumors and kill them, revolutionized how doctors treat children with B cell leukemia (B-ALL). These killer T cells recognize a specific protein expressed on the surface of the leukemic cells. Unfortunately, leukemia frequently relapses and often finds ways to "switch off" the expression of this protein, making T cells unable to track and kill them. This notion is called "antigen escape," as the tumor finds a way to escape the immune treatment. Dr. Aifantis plans to identify ways to avoid antigen escape by boosting the expression of the surface recognition protein. The study aims to validate such mechanisms in an organism using CAR-T cell models and sequencing patient cells. At the same time, Dr. Aifantis will design screens that will help identify surface antigen-specific regulators, so researchers can one day create combinatorial protocols using CAR-T cells and targeting specific antigen surface expression regulators.

This institution is a member of a research consortium which is being funded by St. Baldrick's: New Approaches to Neuroblastoma Therapy (NANT) Consortium. For a description of this project, see the consortium grant made to the lead institution: Children's Hospital Los Angeles, Los Angeles, CA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium. For a description of this project, see the consortium grant made to the lead institution: Baylor College of Medicine, Houston, TX.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium. For a description of this project, see the consortium grant made to the lead institution: Baylor College of Medicine, Houston, TX.

While great strides have been made in treating children with acute leukemia, some children continue to do poorly. For example, children of Hispanic ethnicity are at greater risk of both relapse and treatment-related complications. The Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium will expand and enhance the recently established network of childhood cancer centers, with the goal of tackling ethnic outcome disparities by generating an unmatched resource of clinical information and biological samples. This information will be used to predict those who have the greatest risk of poor outcomes, with a focus on Hispanics, to improve prevention and treatment strategies. Funds administered by Baylor College of Medicine.

This institution is a member of a research consortium which is being funded by St. Baldrick's: New Approaches to Neuroblastoma Therapy (NANT) Consortium. For a description of this project, see the consortium grant made to the lead institution: Children's Hospital Los Angeles, Los Angeles, CA.