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 supports a Clinical Research Coordinator to ensure that more kids can be treated on clinical trials, often their best hope for a cure.

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: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Cellular and Immunological Approaches to Prevent Relapse: Pediatric Blood and Marrow Transplant Consortium (PBMTC). For a description of this project, see the consortium grant made to the lead institution: National Marrow Donor Program, Minneapolis, MN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

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 progress to date, Dr. Wu was awarded a new grant in 2023 to fund an additional year of this Scholar grant. Diffuse midline glioma (DMG) is a fatal brain cancer in children and there are no effective treatments. The brain's natural barrier prevents drugs from reaching the tumor. Focused ultrasound (FUS) uses sound waves to temporarily open the blood brain barrier to increase drug delivery to the protected tumor cells in the brain. As the Hannah's Heroes St. Baldrick's Scholar, Dr. Wu will be using panobinostat, a promising drug tested in cancer cells in the laboratory to examine if FUS can increase its delivery and whether the addition of radiation can further improve the outcomes.

The 2023 year of this grant is co-funded by the Focused Ultrasound Foundation.

The 2021 and 2022 years of this grant are funded by and named for Hannah’s Heroes, a St. Baldrick's Hero Fund established to honor Hannah Meeson. At age six she was diagnosed with anaplastic medulloblastoma. After a relapse and several additional months of treatment, Hannah currently shows no evidence of disease. Throughout her treatments, Hannah never complained and remained positive and happy. This fund pays tribute to her fight by raising awareness and funding for all childhood cancers because kids like Hannah “are worth fighting for.”

This institution is a member of a research consortium which is being funded by St. Baldrick's: North American Consortium for Histiocytosis (NACHO). For a description of this project, see the consortium grant made to the lead institution: St. Jude Children's Research Hospital, Memphis, TN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: North American Consortium for Histiocytosis (NACHO). For a description of this project, see the consortium grant made to the lead institution: St. Jude Children's Research Hospital, Memphis, TN.

This institution is a member of a research consortium which is being funded by St. Baldrick's: North American Consortium for Histiocytosis (NACHO). For a description of this project, see the consortium grant made to the lead institution: St. Jude Children's Research Hospital, Memphis, TN.

This institution is a member of the Children's Oncology Group (COG). From the first event in 2000 until 2004, St. Baldrick's funds benefited the COG. Since the St. Baldrick's Foundation began making grants in 2005, each of the 200 member institutions of the COG has received a portion of a multi-million dollar St. Baldrick's grant every year. These funds have been distributed based on the number of patients at each institution who are treated on COG clinical trials, their best hope for a cure.

This institution is a member of the Children's Oncology Group (COG). From the first event in 2000 until 2004, St. Baldrick's funds benefited the COG. Since the St. Baldrick's Foundation began making grants in 2005, each of the 200 member institutions of the COG has received a portion of a multi-million dollar St. Baldrick's grant every year. These funds have been distributed based on the number of patients at each institution who are treated on COG clinical trials, their best hope for a cure.

This institution is a member of the Children's Oncology Group (COG). From the first event in 2000 until 2004, St. Baldrick's funds benefited the COG. Since the St. Baldrick's Foundation began making grants in 2005, each of the 200 member institutions of the COG has received a portion of a multi-million dollar St. Baldrick's grant every year. These funds have been distributed based on the number of patients at each institution who are treated on COG clinical trials, their best hope for a cure.

This institution is a member of the Children's Oncology Group (COG). From the first event in 2000 until 2004, St. Baldrick's funds benefited the COG. Since the St. Baldrick's Foundation began making grants in 2005, each of the 200 member institutions of the COG has received a portion of a multi-million dollar St. Baldrick's grant every year. These funds have been distributed based on the number of patients at each institution who are treated on COG clinical trials, their best hope for a cure.

This institution is a member of the Children's Oncology Group (COG). From the first event in 2000 until 2004, St. Baldrick's funds benefited the COG. Since the St. Baldrick's Foundation began making grants in 2005, each of the 200 member institutions of the COG has received a portion of a multi-million dollar St. Baldrick's grant every year. These funds have been distributed based on the number of patients at each institution who are treated on COG clinical trials, their best hope for a cure.