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Alex’s Lemonade Stand Foundation Announces 2021 Reach Grant Recipients

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The Reach Grant provides critical funding to propel childhood cancer research from the lab toward clinical trial.

Philadelphia, PA (November 10, 2021) – 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 2021 Reach Grant will support Ching Lau, MD/PhD of Connecticut Children’s Medical Center Foundation; David Daniels, MD/PhD of Mayo Clinic; Ernesto Guccione, PhD of Icahn School of Medicine at Mount Sinai; Kelly Goldsmith, MD of Emory University of School of Medicine; and Loren Walensky, MD/PhD of Dana-Farber Cancer Institute.

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 novel genomic diagnostics for intracranial germ cell tumors, using convection-enhanced delivery of drugs directly into the tumors as targeted therapy, and using Gamma Delta CAR T cell as a novel cellular immunotherapy for patients with neuroblastoma. 

The support of the ALSF Reach Award will allow us to continue to explore and offer novel cellular therapy options for patients with high risk and recurrent neuroblastoma,” Dr. Kelly Goldsmith, Emory University School of Medicine

“The ALSF Reach Grant is essential to our ability to develop and validate entirely new treatments for the hardest-to-treat pediatric cancers,” said Dr. Loren Walensky, Dana-Farber Cancer Institute.

Full summaries of all projects are included on the following page.

“There are significant barriers that make translating innovative ideas to the clinic very difficult. Our Reach Grant seeks to remove one of these barriers by providing support for necessary preclinical work. The support of late-translational studies is integral in finding less toxic treatments and new cures for children with cancer,” said Liz Scott, Co-Executive Director of ALSF.

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.

2021 Reach Grant Recipients

Ching Lau, MD/PhD – Connecticut Children’s Medical Center Foundation, Inc

Novel Genomic Diagnostics for Intracranial Germ Cell Tumors

Germ cell tumors (GCTs) are rare tumors that occur in various locations including the brain. Intracranial GCTs (IGCTs) can be divided into germinomas and nongerminomatous germ cell tumors (NGGCTs) with NGGCTs further divided into five subtypes. IGCTs can be treated with various combinations of chemotherapy and radiotherapy with the germinomas having better response than NGGCTs. Because these tumors are found deep in the brain, obtaining a biopsy for diagnosis is very challenging and risky. So we rely on measuring the levels of two proteins, AFP and β-HCG, in the blood or the cerebrospinal fluid (CSF) to help distinguish germinomas and NGGCTs. Unfortunately, these two proteins can only help diagnose some of the subtypes of NGGCTs but not germinomas and other subtypes of NGGCTs. Therefore, there is an urgent need to identify other diagnostic markers to improve the correct diagnosis of IGCTs. We have found that microRNAs and DNA methylation profiling in CSF could significantly improve our diagnostic capabilities of IGCTs. Because these are very rare tumors, we formed a consortium of 19 children’s hospitals to combine our cases together to carry out a definitive study that will test the effectiveness of these two new tests in the clinical setting. Once they are established, these two tests would become part of the new standards in diagnosing these tumors and move the upcoming clinical trials of the Children’s Oncology Group (COG) forward with confidence.

Loren Walensky, MD/PhD – Dana-Farber Cancer Institute

Stapled Peptide PROTAC: A 3-in-1 Treatment for Pediatric Solid Tumors

Cancer is the leading cause of death by a disease in children ages 0-19 years old. Whereas cure rates for pediatric hematologic malignancies as a class can reach 90% or more, solid tumor cures have historically lagged and contribute disproportionately to the cancer death rate in children. A common mechanism among relapsed and treatment-resistant pediatric solid tumors is a combination of errant signaling that drives cancer cell proliferation and blocks cancer cell death. Thus, multiagent treatment that addresses multiple cancer-causing pathways is required. However, advancing new anti-cancer drug candidates, especially in combination, is especially challenging in children. First, concerns about unanticipated toxicities have long led regulators to require clinical testing in adults before children, causing considerable delays in initiating Phase 1 trials in pediatric cancer. Second, new agents must initially show safety and activity as a single agent before being applied in combination. Third, identifying effective combinations and then brokering clinical testing agreements that bring companies and their proprietary drugs together remains a formidable, logistical barrier. Finally, individual drugs have distinct properties that from a practical standpoint can thwart the delivery of both agents to the same cancer cell at the same time. Here, we combine two technologies to create a single drug that can simultaneously target three key cancer-causing mechanisms of pediatric solid tumors, effectively overcoming major barriers to clinical translation.

Kelly Goldsmith, MD – Emory University School of Medicine

Co-PI: H. Trent Spencer, PhD, Emory School of Medicine
Co-PI: Chris B. Doering, PhD, Emory School of Medicine

Dual PTK7/GD2 Gamma Delta CAR T Cell Therapy for Neuroblastoma

Neuroblastoma is a deadly solid tumor of childhood and current therapy for high-risk disease has many long-term side effects. We therefore need new treatment that kills tumor cells but not normal cells. Most immunotherapy approaches use the patient’s own immune system to fight their tumor. “Cellular” immunotherapy works by taking blood from the patient, isolating certain infection-killing white blood cells, growing them up outside the body, engineering them to recognize the tumor, then infusing them back into the patient to kill their tumor. White blood cells called alpha-beta (αβ) T cells have been used this way in cancer patients (for example, CAR-T therapy for leukemias), but do not work well for pediatric solid tumors like neuroblastoma. Patient αβ T cells are also worn down by chemotherapy and therefore are not the best source for making a cell therapy product. A different white blood cell called a gamma delta (γδ) T cells, can directly kill neuroblastoma cells and can be taken from a healthy donor and safely given to a patient. We propose to use γδ T cells as a novel cellular immunotherapy for patients with neuroblastoma. We have developed a safer strategy to isolate and grow γδ T cells for human use. In the lab, we have shown that γδ T cells improve cancer killing by low dose chemotherapy and help tumor-targeting antibody therapies like the GD2 antibody dinutuximab to kill neuroblastoma tumors. This work led to a first in human clinical trial of healthy donor gamma delta T cells for patients with refractory/relapsed neuroblastoma.

Ernesto Guccione, PhD – Icahn School of Medicine at Mount Sinai

Co-PI: Josep Llovet, MD, Icahn School of Medicine at Mount Sinai
Co-PI: Arvin Dar, PhD, Icahn School of Medicine at Mount Sinai

IND-enabling Studies for WNTinib, a Novel Selective Therapeutic for CTNNB1 Mutant Hepatoblastomas

Hepatoblastoma (HB) is the most frequent pediatric form of liver cancer, generally arising in young children (<3yo). Despite being a rare tumor (1.8 in 1,000,000 children/year), HB rates are on the rise and therapeutic options are limited to chemotherapy. Chemotherapy (i.e. cisplatin) is given to patients without any consideration to a specific mutation within tumors and toxicity is significant. Here we seek to advance a novel therapeutic candidate for HB that has been optimized to selectively kill cancer cells with specific mutations, while sparing normal hepatocites. In this proposal, we plan to advance through to clinical trials, a new small molecule, that we named WNTinib. This compound has demonstrated strong activity in hepatoblastomas with a specific mutation in the CTNNB1 gene, which occurs in 70% of HB cases, suggesting potentially broad utility of this compound as a precision medicine for HB. The major goal of the grant is to test WNTinib alone or in combination with current standard of care therapies, such as cisplatin, for CTNNB1 mutant HB patients. In particular we will assess the efficacy and safety of WNTinib using preclinical models and patient derived samples. Based on the proposed preclinical experiments, we will be able to suggest stratification strategies and identify more effective tailored therapeutics for HB.

David Daniels, MD/PhD – Mayo Clinic

Optimization of Drug Efflux and Brain Clearance to Improve CED of Targeted Therapy to H3K27M DMG

Brain tumors are the leading cause of cancer-related deaths in children. Amongst those, high-grade brainstem tumors known as diffuse midline gliomas, are the most aggressive and uniformly deadly. Radiation therapy is the only treatment option, but only extends life a few months. Most children typically succumb to disease within 12 months of diagnosis. Attempts at chemotherapy have failed in part due to the blood brain barrier, which prevents drugs from getting to the tumor. Therefore, methods to deliver drugs by bypassing the blood brain barrier are of great interest. Convection-enhanced delivery overcomes the blood brain barrier through a direct injection under a pressure gradient into the tumor region. This technique has been shown to be safe in children with these tumors but has not yet achieved its maximum therapeutic potential.

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.