Alex’s Lemonade Stand Foundation Announces 2018 Reach Grant Recipients 

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

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 three leading institutions across the country. The Reach Grant provides much-needed funding at a critical point in the development of a cancer therapy – preparation for FDA approval. Each recipient will receive up to $250,000 over the course of two years.

The 2018 Reach Grant will support Rintaro Hashizume, MD/PhD of Northwestern University; Eric H. Raabe, MD/PhD of The Johns Hopkins University School of Medicine; and Soheil Meshinchi, MD/PhD of Fred Hutchinson Cancer Research Center.

Dr. Hashizume and his co-investigator Dr. Ali Zhang’s project will study a therapeutic target for atypical teratoid/rhabdoid tumor (AT/RT), a highly-malignant brain tumor with poor prognosis despite aggressive treatments. Dr. Raabe and his co-investigators Dr. Kristine Glunde, Dr. Barbara Slusher and Dr. Charles Eberhart will study possible drug combinations with an already existing drug TAK228 to treat pediatric brain tumors. Dr. Meshinchi and his co-investigator Dr. Colin Correnti will study if an already existing immunotherapy can be repurposed to treat acute myeloid leukemia in children younger than 3.

Full summaries of all projects are included below.

“ALSF is committed to accelerating breakthrough treatments for kids with cancer,” said Liz Scott, co-executive director of ALSF. “Through our Reach Grant program, we invest in research that will lead to clinical trials to ensure impact for children facing this disease 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.

2018 Reach Grant Recipients

Rintaro Hashizume, MD/PhD – Northwestern University
Co-investigator: Dr. Ali Zhang
Epigenetic Targeted Therapy and Resistance in Pediatric Rhabdoid Tumor

Background
The pediatric rhabdoid tumor, atypical teratoid/rhabdoid tumor (AT/RT), is a highly-malignant brain tumor that has a poor prognosis despite aggressive treatment. The development of new, effective therapeutic approaches for AT/RT has been hindered by a lack of specific therapeutic targets. It is necessary to find effective therapeutic targets, preferably based on the understanding of the molecular mechanisms that promote this highly-malignant brain tumor. A tumor-suppressor gene (SMARCB1) is absent in the majority of AT/RT and loss of this gene leads to increased activity of histone-binding proteins and promotes tumor growth. The research involving pharmacologic inhibition of histone-binding proteins, EZH2 and BRD4, is of high importance for developing effective therapies for AT/RT. Recently published results indicate the abnormal activity of the histone binding proteins (EZH2 and BRD4) with absence of the tumor-suppressor gene (SMARCB1) is fundamental to the occurrence of AT/RT.

Project Goal
The goal of this project is to determine whether the therapeutic combination of targeting histone-binding proteins, BRD4 and EZH2, provides synergistic benefits. It will inform how to best maximize the clinical potential of combination therapy for effective treatment of children with AT/RT. This research will also test how tumors adapt to molecular-targeted therapy that will ultimately inform clinicians how to treat tumors that have resistance to this kind of therapy. Finally, this project will explore how our combination therapy interacts with radiation in treating AT/RT, which is important due to the frequent use of radiation in treatment.   

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Eric H. Raabe, MD/PhD – The Johns Hopkins University School of Medicine
Co-investigators: Dr. Kristine Glunde, Dr. Barbara Slusher and Dr. Charles Eberhart
Identifying a Therapeutic Partner for TAK228 for Pediatric Phase II Brain Tumor Studies

Background
The goal of this proposal is to find new drugs that work together to kill pediatric brain tumor cells. As part of a previous Alex’s Lemonade Stand Foundation project, we found that a drug called TAK228 could kill pediatric brain tumor cells. This drug gets into the brain well and is currently in clinical trials in adults for breast and other cancer types. We found that TAK228 works well with some therapies we currently use in pediatric brain tumors. But those therapies may be too toxic for patients who have relapsed or refractory disease and who have already received heavy doses of chemotherapy and radiation.

Project Goal
We now propose to use our knowledge of the biology of TAK228 as well as the ways that cancer cell metabolism differs from normal cells to find new agents that could combine with TAK228 to kill pediatric brain tumor cells and spare normal cells. TAK228 is currently in the planning stages for a US-government-funded phase I study in pediatric brain tumors. At the end of this grant, we anticipate that we will have discovered at least one new drug that can be combined with TAK228 in phase II studies for patients with relapsed or refractory pediatric brain tumors.            

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Soheil Meshinchi, MD/PhD – Fred Hutchinson Cancer Research Center
Co-investigator: Dr. Colin Correnti
Immuno-therapeutic Targeting of CD56 in CBA2T3/GLIS2-AML in Children

Background
Acute myeloid leukemia (AML) is a particularly devastating disease in infants, where therapies that are intended to cure leukemia frequently fail to cure the disease and lead to significant life-limiting or life-ending complications. Leukemia-specific targeted therapies are critical especially in these most vulnerable patients in order to cure the disease without causing irreversible damage to their growing body. Through the largest and most detailed sequencing studies, we have identified a genetic abnormality that is only seen in children younger than 3 years of age. This genetic alteration called CBF/GLIS causes a lack of response to all available therapies, and more than 80% of babies with this mutation die of leukemia despite receiving intensive chemotherapy. We have discovered that leukemic cells in babies with CBF/GLIS express a protein called CD56 at high levels. Expression of this protein on the leukemia cells provides an opportunity for targeting the leukemic cells with immunotherapy. Fortunately, one such immunotherapy (called antibody-drug conjugates; CD56-ADCs) has been developed for other diseases that can be repurposed for use in AML. We can also create new immunotherapies against CD56.

Project Goal
In this project, we will test the ability of available CD56-ADCs to kill CBF/GLIS-positive AML cells as well as create a novel immunotherapy, called bi-specific (BITE) or multi-specific immunotherapies, against CD56. We are highly optimistic that given the high CD56 expression on leukemic cells, we can rapidly identify or create new immunotherapies for infants with high-risk AML.

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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 amount 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. Every day, approximately 250 kids around the world die from cancer, accounting for 91,250 losing their lives to the disease every year.

About Alex’s Lemonade Stand Foundation
Alex's Lemonade Stand Foundation (ALSF) emerged from the front yard lemonade stand of cancer patient Alexandra “Alex” Scott (1996-2004). In 2000, 4-year-old Alex announced that she wanted to hold a lemonade stand to raise money to help find a cure for all children with cancer. Since Alex held that first stand, the Foundation bearing her name has evolved into a national fundraising movement, complete with thousands of supporters across the country carrying on her legacy of hope. To date, Alex’s Lemonade Stand Foundation, a registered 501(c)3 charity, has raised more than $150 million toward fulfilling Alex’s dream of finding a cure, funding nearly 1,000 pediatric cancer research projects nationally. In addition, ALSF provides support to families affected by childhood cancer through programs such as Travel For Care and SuperSibs. For more information on Alex’s Lemonade Stand Foundation, visit AlexsLemonade.org.