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The Reach Grant provides critical funding to propel childhood cancer research from the lab toward clinical trial.
Philadelphia, PA (March 4, 2020) – Alex’s Lemonade Stand Foundation (ALSF), a nonprofit dedicated to finding cures for all children with cancer, awarded Reach Grants to childhood cancer researchers at five leading institutions across the country. The Reach Grant provides much-needed funding at a critical point in the development of a cancer therapy – obtaining the preclinical data needed to support the initiation of a clinical trial. Each recipient will receive up to $250,000 over the course of two years.
The 2019 Reach Grant will support Alice Bertaina, MD/PhD of Stanford University School of Medicine; Garrett Brodeur, MD of Children’s Hospital of Philadelphia; Dean Lee, MD/PhD of Nationwide Children’s Hospital; Linda Malkas, PhD of City of Hope Beckman Research Institute; and Danny Reinberg, PhD of NYU School of Medicine.
The Reach Grant recipients will test innovative approaches to improve the way childhood cancers are treated with the goal of moving less toxic, more efficacious therapies into clinical trial. The approaches include using donor-derived CAR T cells to seek and destroy cancer cells, using a novel nanoparticle drug-delivery system to increase the concentration of drug in tumors compared to healthy tissue, and developing and testing new targeted small molecule inhibitors.
“More effective, less toxic therapy is needed for children with high-risk solid tumors. The nanomolecular formulation we have developed can deliver 100 times the effective dose of chemotherapy to tumors compared to an equivalent dose as a conventional drug, so it is much more effective. There is also less toxicity, as less total drug can be given,” said Garrett Brodeur, MD, Professor of Pediatrics at Children’s Hospital of Philadelphia. “This grant will allow us to conduct the additional preclinical studies necessary to bring this novel agent to clinical trial. This will provide a valuable alternative to treat virtually any solid tumor in children.”
Full summaries of all projects are included on the following page.
“ALSF is committed to funding research that will contribute to better, less toxic breakthrough treatments for childhood cancer and save lives,” said Liz Scott, co-executive director of ALSF. “Our Reach Grant program allows us to invest in research that will lead to clinical trials to ensure impact for childhood cancer heroes and their families.”
The aim of the Reach Grant is to fund studies which will result in the initiation of a clinical trial within a short time period, ideally two to three years. For more information about the Reach Grant or Alex’s Lemonade Stand Foundation’s various grant categories and successes, visit ALSFgrants.org.
2019 Reach Grant Recipients
Alice Bertaina, MD/PhD – Stanford University School of Medicine
Optimizing TCRaB+/CD19+-depleted Haploidentical HSCT for ALL using Donor-derived Genome-edited CAR T Cells
Blood stem cell transplantation can cure acute lymphoblastic leukemia (ALL) in children who have no other treatment options. Traditionally, this has not been available for all patients because of the need for stem cell donors that are compatible; however, a novel procedure has been developed in which T cells that could attack patient cells in case of a mismatched transplant are removed before the infusion. This strategy allows transplantation from partially matched donors greatly expanding the number of patients who can benefit. However, some patients still relapse after the transplant. To improve outcomes, scientists have developed “CAR T cells” by taking a patient’s own T cells and engineering them to kill only leukemia cells. We have developed an innovative approach to improve CAR T cell production and broaden its accessibility. Instead of using patient T cells, we repurpose donor T cells that are separated from the stem cells and otherwise discarded, delete the gene responsible for potential negative effects on the recipient, and replace that gene with a new gene that reprograms the cells to kill leukemia cells. We aim to create a potent treatment for high risk ALL, eradicating leukemic cells without increasing the risk for side effects.
Garrett Brodeur, MD – Children’s Hospital of Philadelphia
Multivalent Nanomedicine to Treat High-risk Pediatric Solid Tumors
Current therapy for high-risk pediatric solid tumors like neuroblastoma and sarcomas requires extremely intense treatment. However, cure rates are <50%, and there are significant long-term side effects in survivors. Targeted delivery of anticancer agents using nanomedicines can dramatically improve efficacy and reduce systemic toxicity because nanomedicines easily pass through the leaky blood vessels of tumors but not most normal blood vessels so more drug gets to the tumor than the rest of the body. In this proposal, a novel drug called SN22 will be tested. A novel nanomedicine delivery system that carries four copies of SN22 has been developed, and the antitumor effects as well as toxicity will be tested in mouse models of neuroblastoma, Ewing sarcoma, rhabdomyosarcoma and osteosarcoma to show efficacy in other pediatric solid tumors. The successful completion of these studies will inform a phase 1 clinical trial for recurrent or refractory solid tumors in children.
Dean Lee, MD/PhD – Nationwide Children’s Hospital
Generation of CMV-specific CD19 CAR T cells Using Cytokine Capture Followed by Lentiviral Transduction and Expansion
Pediatric leukemia remains the second leading cause of cancer death in children. While outcomes for newly diagnosed patients have dramatically improved in the last several decades, response rates for relapsed acute lymphoblastic leukemia remain <50%. Chimeric antigen receptor (CAR) T cells are immune cells that are taken out of the body and genetically changed to attack cancer cells. The patient’s cells are affected by chemotherapy medications and can be both low in number and not function as well as a healthy person’s immune cells. For this reason, many patients are unable to receive this potentially lifesaving therapy. Our goal is to use immune cells from the patient’s parent to make CAR T cells that will specifically target the leukemia cancer cells. The parental cells will be processed on a machine that selects out immune cells that are specific for a virus. We will then generate CAR T cells from the virus-specific cells to be delivered to the patient. Successful funding of this project will allow us to generate the pre-clinical data required by the FDA before giving these experimental cells to patients.
Linda Malkas, PhD – City of Hope Beckman Research Institute
Preclinical Development of a First-in-class PCNA Inhibitor for Treating Neuroblastoma
This project is focused on developing a safe and effective therapy for treating high-risk neuroblastoma (NB). NB is one of the most common childhood neoplasms and accounts for 15% of all pediatric cancer deaths. The single most important factor determining the treatment options and prognosis of NB patients is risk stratification. Survival is excellent in low- and intermediate-risk groups. In contrast, there is currently no effective treatment for high-risk NB, in part because of a limited drug development effort for this disease type. We discovered a novel small molecule, AOH1996, that selectively targets a cancer-associated protein isoform and effectively inhibits the growth of NB tumors but causes no observable side-effects. Here, we propose to perform a comprehensive toxicology study on AOH1996 according to the FDA’s guidelines. Such a study is critical to gain regulatory approval to start clinical trials.
Danny Reinberg, PhD – NYU School of Medicine
Targeting a Novel Epigenetic Signature in Diffuse Intrinsic Pontine Gliomas
Diffuse Intrinsic Pontine Gliomas (DIPGs) are the most lethal of all pediatric brain cancers with a survival rate of less than 2 years for most children. Genetic profiling has revealed that over 85% of DIPGs acquire a specific dominant-negative mutation in one of the 15 copies of histone H3 genes that encode the proteins that package their DNA genomes into chromatin which effects the expression of the genes that they package. We identified one such modification (H3K36me2) that is massively elevated in DIPG tumor cells. In addition, we discovered the proteins that specifically bind this modification and uncovered their basic biological function: they maintain the expression of genes found in the chromatin to which they are bound. With chemists at The University of Toronto, we have developed preliminary compounds that block the ability of these proteins to bind to this modification. We will work to develop compounds that inhibit the enzymes that cause the elevation of this modification. Further in vivo testing of these compounds in transgenic mice engineered with DIPG tumors will be carried out at NYU.
About Childhood Cancer
Childhood cancer is a general term used to describe cancer in children occurring regularly, randomly and sparing no ethnic group, socioeconomic class, or geographic region. Childhood cancer extends to over a dozen types of cancers and a countless number of subtypes. Just a few of these cancer types include Ewing sarcoma, glioma, leukemia, lymphoma, medulloblastoma, neuroblastoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma and Wilms’ tumor. In the United States, childhood cancer is the leading cause of death by disease in children under the age of 19.
About Alex’s Lemonade Stand Foundation
Alex's Lemonade Stand Foundation (ALSF) emerged from the front yard lemonade stand of 4-year-old Alexandra “Alex” Scott, who was fighting cancer and wanted to raise money to find cures for all children with cancer. Her spirit and determination inspired others to support her cause, and when she passed away at the age of 8, she had raised $1 million. Since then, the Foundation bearing her name has evolved into a national fundraising movement. Today, ALSF is one of the leading funders of pediatric cancer research in the U.S. and Canada raising more than $200 million so far, funding nearly 1,000 research projects and providing programs to families affected by childhood cancer. For more information, visit AlexsLemonade.org.