Cookies for Kids' Cancer - 2020 Childhood Cancer Research Grant Recipients
Cookies for Kids’ Cancer has granted over $17 million to date, funding over 100 research projects that have resulted in 25 treatments and clinical trials available to children today.
Our all-star Medical Advisory Board meets each year to review and evaluate grant requests using the same stringent criteria as the National Cancer Institute. We want to fund the best and most promising research that will help children as soon as possible.
Here are the grants our supporters made possible in 2020:
Fred Hutchinson Cancer Research Center/Seattle Children’s Hospital: $100,000 Grant
Project: Advanced Molecular Monitoring of CAR T cell therapy for diffuse midline gliomas
Recipient: Nicholas A. Vitanza, MD
Diffuse midline gliomas with H3 K27M mutations (DMG), including diffuse intrinsic pontine glioma (DIPG), are fatal tumors that occur in unresectable parts of the central nervous system (CNS), which includes the brain and spine. They most commonly occur in children 6 years of age and the median survival is only 11 months. Seattle Children’s Vitanza Lab is dedicated to studying this disease with the goal of improving the lives of children with DMG and ultimately curing this disease.
Chimeric antigen receptor (CAR) T cells are a specific type of immunotherapy built from a patient’s own immune system and have been incredibly successful in curing relapsed leukemia in children. At Seattle Children’s, we have treated over 300 children with CAR T cells for a range of cancers and have 3 open trials dedicated to pediatric CNS tumors.
Through a powerful collaboration with The Translational Genomic Research Institute (TGen), we can get results both from our laboratory models after they are treated with CAR T cells and in patients who are enrolled in CAR T cell trials for children with recurrent CNS tumors and DMG.
Children’s Hospital of Philadelphia: $100,000 grant
Project: Understanding mechanisms and developing therapies for MN1-driven leukemia
Recipient: Kathrin M. Bernt, MD
Our group recently discovered how a protein called Meningioma-1 (MN1) causes cancer. We found that in some leukemias, the MN1 gene breaks and becomes attached to another chromosome where it is put into overdrive. In parallel, another group found that this also happens in a subset of pediatric brain cancers. MN1 is a bit of a mystery protein – it has been very unclear what it actually does. MN1 is very sticky. We found that it is this “stickiness” than is central to MN1 ability to cause cancer. By gumming up some of the machinery that normally regulates the development of immature cells in the bone marrow to mature blood cells, MN1 forces cells to remain in an immature state, expand, and crowd out mature functioning cells. This is the definition of leukemia.
Now that we understand what MN1 does, we need to figure out a way to inhibit it. The goal of the project supported by Cookies for Kids Cancer is to identify means to block the sticky protein – either by figuring out what makes it sticky and blocking it directly (aim 1), or by blocking the proteins it sticks to (aim 2).
University of California San Francisco Benioff Children’s Hospital: $100,000 grant
Project: Exploiting therapeutic opportunities against high-risk leukemias harboring TP53 mutations
Recipient: Ernesto Diaz-Flores PhD
In my group, we study hypodiploid B cell leukemia (LH B-ALL), an aggressive and deadly childhood cancer, affecting kids 1-10 years old, characterized by less than 43 chromosomes, and high mortality rate (5-year event free-survival <29% compared to >85% for leukemia patients overall).
90% of patients present mutations in a gene called TP53, and 40 % of them present it at birth, representing a type of Li-Fraumeni syndrome, the most common cancer predisposition syndrome. Neither intensive chemotherapy nor hematopoietic stem cell transplant improve survival in these patients who even relapse with CAR-T cell therapy, stressing the urgent need for new curative strategies.
With our treatment strategy we aim to eliminate only the p53 mutant leukemic cells, while minimizing any off-target toxicity. We hope this strategy will turn this highly deadly cancer into a highly curable one.
St. Jude Children's Research Hospital: $100,000 grant
Project: Targeting the p53 pathway in high risk pediatric atypical teratoid rhabdoid tumors
Recipient: Martine F Roussel, PhD
Atypical teratoid rhabdoid tumor or ATRT is a particularly devastating disease that occurs mainly in the brain and, very rarely in the spinal cord of very young children - it is heartbreaking. Though an extremely rare form of cancer in children, with approximately 75 children being diagnosed annually in the United states, majority of them are less than 3 years of age at diagnosis. This makes it particularly challenging to cure ATRT due to the risk of side effects from radiation therapy on the growing brain. The failure rate for the currently available treatments are approximately 70% depending upon the age of presentation of the disease.
Because of this, we decided as a group to find new ways to treat ATRT and other similarly aggressive brain tumors which could potentially be more effective and have less side effects on the children. We have developed several patient-derived xenografts that are tumors from patients with ATRT treated at St. Jude that we immortalize in the brain of immuno-compromised mice.
We first undertook drug screens in cell lines that identified compounds that when added in combination profoundly suppressed tumor growth in vitro. One such drug is a MDM2 inhibitor that prevents P53 from being degraded thus inducing p53-induced cell death. Additionally, we found that another drug called Selinexor, that activates p53 pathway by an alternate mechanism by preventing its nuclear exit, when combined with the MDM2 inhibitor drug, acts synergistically and enhances tumor cell death. With these in vitro data on hand, we confirmed that the drugs crossed the blood brain barrier. Ongoing experiments with these drugs when used either as single agent and in combination in mice that carry patient-derived xenografts demonstrate encouraging preliminary data.
This grant will allow us to expand these pre-clinical studies in mice and confirm the preliminary results with the eventual goal of developing clinical trials using novel combinations of drugs at St. Jude for children with these highly aggressive and often fatal brain tumors. We also hope to identify other drug combinations that we will test pre-clinically.
Texas Children’s Cancer Center/Baylor College of Medicine: $100,000 grant
Project: Targeting PAK4 in high-risk rhabdomyosarcoma
Recipient: Dr. Jason Yustein
Rhabdomyosarcoma is the most common soft tissue sarcoma, or tumor of the muscle, in childhood. Overall, the treatments for rhabdomyosarcoma include chemotherapy, surgery and/or radiation, which have improved overall survival rates to approximately 65-70%. However, despite strengthening therapeutic regimens, long-term outcomes for patients with metastatic or relapsed rhabdomyosarcoma remain extremely poor, with overall survival rates between 20-30%.Thus, alternative therapies, or combination therapies are essential for improving outcomes. For rhabdomyosarcoma, activation of vital cell pathways drive resistance to chemotherapy and successful spread of disease, which is known as metastasis. Our laboratory has recently identified that a family of kinases, which are key enzymes in cells, known as the p21-activated kinases (PAKs) are activated and promote aggressive properties in rhabdomyosarcoma.
PAKs control several key cancer-causing pathways. Our lab has identified PAK4 as a critical regulator of cancer-related signaling pathways in rhabdomyosarcoma. We have preliminary genetic and small molecule studies providing evidence that targeting PAK4 inhibits tumor promoting and metastatic conditions in rhabdomyosarcoma. The overarching goals of our proposal are to study the treatment benefit of targeting PAK4. Specifically, our proposal will study the effectiveness of clinically relevant therapies using human and mouse rhabdomyosarcoma models. We believe using PAK4 targeting agents, which are actively being used in clinical trials, can provide effective treatments for these high-risk patients. Completion of these studies is expected to provide new therapies that can quickly move to clinical trial for the treatment of relapsed and metastatic sarcomas.
Dana-Farber Cancer Institute/The Jimmy Fund: $100,000 grant
Project: Augmenting immune response in neuroblastoma
Recipient: Dr. Rani George, MD, PhD
The success of immune-based treatment in adult cancers has not extended to neuroblastoma. We have identified that many of the genes that induce an immune response in neuroblastoma are epigenetically suppressed. With this support, my team aims to investigate whether pre-treatment of neuroblastoma cells with small molecule inhibitors of the PRC2 repressor complex can cause the immune response genes to be reactivated. If successful, the results of our research would help counter the ability of neuroblastoma cells to suppress the immune system and revise treatments now in use against high-risk neuroblastoma. With full lives ahead of them, our young patients deserve to have durable treatments that spare them so many of the toxic and late effects of traditional treatment.
Texas Children’s Cancer Center/Baylor College of Medicine: $100,000 grant
Project: Development of a human natural killer cell immunotherapy against pediatric sarcomas
Recipient: Dr. Robin Parihar
Treatments using the immune system to fight childhood bone and muscle tumors (sarcomas) have shown promise in the lab. However, their ability to cure patients has been limited by a powerful tumor environment that turns off the immune system and does damage to normal cells. We have developed a cancer therapy that uses natural killer (NK) cells, a type of white blood cell with excellent tumor killing capacity and a unique ability to distinguish normal tissues in the body. The NK cells safely target both the tumor environment and sarcoma-associated proteins in a special way that allows them to destroy cancer but leave normal tissues alone. We will test the ability of these NK cells to kill tumors safely in laboratory models, and then make preparations to test safety and effectiveness in kids with sarcoma.
Despite attempts to improve treatment over the last few decades, children with advanced pediatric sarcoma of muscle or bone continue to die from their disease. New treatments are sorely needed. Treatments that utilize the immune system to fight cancer have shown promise in the lab. Their ability to cure patients, however, has been limited by a powerful tumor environment that turns off the immune system. In addition, because there are very few target proteins specific to sarcoma tumors (i.e., those expressed on the tumor, but not on normal tissues), it is difficult to spare normal cells from damage during immune treatment. Thus, there is a critical need to develop treatments that safely target both the tumor microenvironment (TME) and sarcoma‑associated proteins so that immune treatments can destroy cancer but leave normal tissue alone. To overcome these challenges, we have developed a treatment that utilizes natural killer (NK) cells, a type of immune cell with excellent tumor killing capacity and a unique ability to distinguish normal tissues in the body. To further enhance their activity, we have modified NK cells to target both sarcoma tumor cells and the TME. We are now testing the ability of these NK cells to kill tumors safely in lab models and making regulatory preparations to test safety and effectiveness in children with advanced soft-tissue sarcoma within the context of a clinical trial.
The burden of pediatric cancer, both physical and emotional, for patients and their families is immense. My lab aims to help discover more specific, less toxic treatments to decrease that burden. We expect our research to lead directly to a cell therapy clinical trial at Texas Children’s Hospital for children with soft-tissue and bone sarcomas.
Children’s Oncology Group, Pediatric Early Phase Clinical Trial Network (PEP-CTN): $150,500 grant
Since 2012, we have granted $2,745,300 to the Pediatric Early Phase Clinical Trial Network (PEP-CTN). We match dollar for dollar the funding the National Cancer Institute (NCI) provides for every child enrolled at the 20 participating centers which are located across the country. For three years of our funding, we actually doubled the amount the NCI funds.Here are some figures about the program and our support:
- Last year, support from Cookies for Kids’ Cancer went to 18 institutions for 43 children who enrolled on PEP-CTN studies
- Since 2012, support from Cookies for Kids’ Cancer went to 35 institutions for 828 children who enrolled on early phase studies
- This week, the FDA will grant approval for children for a targeted agent for a rare type of lymphoma based upon a COG phase 1 study
- FDA approval means that children anywhere in the US can get access to a medication that is both effective and has much fewer side effects that standard chemotherapy
- The COG study also evaluated a liquid form of the medication, which is much more kid friendly than large tablets
- With the dedicated COG early phase trial, this would not have happened
Institutions that have received funding from Cookies for Kids’ Cancer in conjunction with PEP-CTN include:
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
C S Mott Children’s Hospital
Cincinnati Children’s Hospital Medical Center
UCSF Medical Center-Mission Bay
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Children’s Hospital of Philadelphia
Riley Hospital for Children
University of Minnesota/Masonic Cancer Center
Children’s Hospital of Alabama
Children’s Healthcare of Atlanta - Egleston
Saint Jude Children’s Research Hospital
Children’s Hospital of Orange County
Children’s Hospital of Pittsburgh of UPMC
Washington University School of Medicine
Children’s National Medical Center
Seattle Children’s Hospital
Dana-Farber/Harvard Cancer Center
Ann and Robert H Lurie Children’s Hospital of Chicago
Children’s Hospital of Colorado
Children’s Hospital of Los Angeles
Children’s Hospital of Wisconsin
Oregon Health and Science University
Hospital for Sick Children
Midwest Children’s Cancer Center
Mark O’Hatfield-Warren Grant Magnuson Clinical Center
Lucile Packard Children’s Hospital Stanford University
University of Oklahoma Health Sciences Center
University of Texas Southwestern Medical Center
Centre Hospitalier Universitaire Sainte-Justine
Children’s Mercy Hospitals and Clinics
Cook Children’s Medical Center
Montefiore Medical Center - Moses Campus
Nemours Children’s Clinic - Jacksonville
Phoenix Children’s Hospital
Rady Children’s Hospital - San Diego
National Institutes of Health Clinical Center
Every year the grants we make are the direct result of hard work, passion and love. This year, in a year of turmoil and uncertainty, that love and passion was even more evident. Thank you for helping make these grants possible.
With your incredible donations, we’re able to continue making meaningful strides in pediatric cancer research.