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Philadelphia, PA (January 6, 2014) – Alex’s Lemonade Stand Foundation (ALSF), a nonprofit dedicated to finding cures for all kids with cancer, has just announced the awarding of five ‘A’ Awards to promising young researchers across the country, totaling $1.875 million in new grants. The grants, which will extend to researchers at Georgia Health Sciences University Institute (Augusta, GA), Huntsman Cancer Institute (Salt Lake City, UT), Memorial Sloan-Kettering Cancer Center (New York, NY), University of Maryland (College Park, MD) & Washington University (St. Louis, MO), are designed for young scientists who want to establish their career in pediatric oncology. Recipients will each receive $375,000 over the course of three years.
The ‘A’ Award joined a prestigious line of medical and nursing grants from Alex’s Lemonade Stand Foundation in 2009 to encourage the best and brightest young researchers to build lifelong careers in the field. Operating under the belief that engaging researchers early in their career leads to long term commitments to find a cure, ALSF works to find and support exceptional early-career researchers.
The 2013 ‘A’ Award recipients are: Theodore Johnson, MD/PhD of Georgia Health Sciences University Research Institute for his research into brain tumors; Kevin Jones, MD of the Huntsman Cancer Institute for alveolar soft part sarcoma research; Alex Kentsis, MD/PhD of Memorial Sloan-Kettering Cancer Center for leukemia/acute myelogenous leukemia (AML) research; Christopher Jewell, PhD of the University of Maryland – College Park for his examination of neuroblastoma; and Jeffrey Bednarski, MD/PhD of Washington University for his study of leukemia/lymphoma. Full lay summaries of the young scientists’ research are included on the following page.
Along with the funds provided to ‘A’ Award recipients ($125,000 per year for 3 years), the award will also include the opportunity to speak and attend Foundation events, reference books to enhance the researcher’s personal pediatric oncology library, equipment to aid in their research (up to $10,000 value) and funding to attend one educational course or event.
“Alex’s Lemonade Stand Foundation has always had a mission of supporting the very best research available, contributing to our ultimate goal of finding a cure for all kids with cancer,” said Jay Scott, Co-Executive Director of Alex’s Lemonade Stand Foundation. “The ‘A’ Awards play an integral role in doing just that, bringing the fresh perspectives of young scientists to the forefront of the field, and keeping them there.”
For more information on the ‘A’ Award, or Alex’s Lemonade Stand Foundation’s various grant categories and successes, visit: www.ALSFgrants.org.
Alex’s Lemonade Stand Foundation 2013 ‘A’ Award Grant Recipients
Theodore Johnson, MD/PhD, Georgia Health Sciences University, Augusta, GA
IDO-based Immunotherapy for Pediatric Brain Tumors
This proposal will address a fundamental gap in understanding the specialized immune biology of the brain tumor micro environment. The applicant is a pediatric oncologist with PhD training in basic molecular immunology who studies the indoleamine 2,3-dioxygenase (IDO) pathway of immune tolerance. IDO is often co-opted by tumors to escape immune attack. Immunologic therapy of cancer is now a cutting-edge new form of cancer treatment for adults, but has not yet brought benefit to children with cancer. The long-term goal is for the applicant to establish a pediatric immunotherapy program to translate pediatric-focused laboratory research into Phase I and Phase II immunotherapy trials in children. The objective of the current proposal is to elucidate the mechanisms by which blocking IDO synergizes with standard chemotherapy and radiation therapy. The proposed research plan builds on the applicant's preliminary data that intense inflammation plays a key role in tumor destruction when IDO-blockade is combined with chemo-radiation therapy in a mouse brain tumor model. The central hypothesis is that IDO is a previously unrecognized vascular quiescence factor in tumor biology and that blocking IDO during chemo-radiation therapy leads to rapid immune-mediated vasculitis and tumor destruction; this widespread innate inflammation then serves as a potent stimulant to drive specific and lasting anti-tumor immunity. The rationale for this research is that understanding the mechanisms by which IDO shields tumors from the underlying immune-activating effects of our standard chemo/radiation therapies will allow us to develop new strategies to combine these standard treatments with immunologic therapy.
Kevin Jones, MD, Huntsman Cancer Institute, Salt Lake City, UT
Targeting Metabolism in Alveolar Soft Part Sarcomagenesis
Every cell generates and consumes energy to perform its functions. This is termed metabolism. One intermediate step in sugar metabolism is a molecule called lactate. Traditionally, lactate was considered only a by-product of metabolism in tissues with low oxygen levels. This view was overturned when scientists learned that some cells with normal oxygen levels intentionally produce lactate and others consume it as a preferred fuel. Cancer cell metabolism is a growing field of study. The traditional view of cancer cell metabolism emphasized the inefficient consumption of sugar and the production of excess lactate. This view is now challenged by data showing that some cancer cells instead use lactate as a fuel. Further, we now know that lactate also functions as a signal, driving vessel in growth into tumors. What is needed is a model system in which we can test lactate metabolism in a living tumor. Alveolar soft part sarcoma is a deadly cancer that typically arises in the limbs of adolescents or young adults. It is deadly because it spreads to distant sites of the body and is then resistant to all available treatments. The young victims of this disease need better treatment options. Alveolar soft part sarcoma demonstrates signs of dependence on lactate metabolism. With a new model of this disease, we hope to investigate its metabolism as a means of finding novel treatment approaches. If our hypothesis is correct, an entire new avenue of treatment options opens not only for this particular tumor, but for cancer more generally.
Alex Kentsis, MD/PhD, Memorial Sloan-Kettering Cancer Center, New York, NY
Rational Combination Therapy of AML
Acute myeloid leukemia (AML) is a cancer of the blood that affects about 500 children every year in the United States. Current treatment of AML with chemotherapy is toxic, and new therapies are direly needed for children whose disease is resistant to intensive chemotherapy. Our research into molecular signaling pathways that drive leukemia cell survival has revealed a new set of therapeutic targets. The support of Alex's Lemonade Stand Foundation will enable us to determine the precise molecular mechanisms responsible for signaling that sustains AML cell growth. We will then use this knowledge to rationally devise combination treatments to block AML signaling and effect cure.
Christopher Jewell, PhD, University of Maryland – College Park, College Park, MD
Engineering the Lymph Node Environment with Therapeutic Vaccine Depots to Combat Neuroblastoma
Neuroblastoma is one of the most common cancers in young children, and current treatments for moderate and high risks patients are often ineffective. When tumors are cleared, drug therapy often leaves patients with lasting side effects or relapse occurs. However, therapeutic vaccines have recently demonstrated potential for combating neuroblastoma or other cancers. To effectively combat tumors, therapeutic vaccines must generate potent tumor-specific immune responses that are functional in the immunosuppressive tumor environment, and that are able to resist tumor regrowth during relapse. An increasingly important challenge for the vaccine field is design of vaccines that generate immune responses with characteristics optimized to combat target diseases such as neuroblastoma. In contrast to broadly-acting drugs or chemotherapy, these designer vaccines could offer highly-specific, immune-based treatments. Establishing strong immunological memory cells specific for tumors has recently been described as a potential route to improve cancer vaccines. These cells exhibit high anti-tumor activity and can combat relapse that occurs after initial tumors are cleared. Unfortunately generating these cells is challenging. In this proposal we will combine direct lymph node delivery with engineered biomaterial vaccines loaded with signals to induce these immune memory cells. Lymph nodes are the tissues that coordinate immune response and controlled delivery of cancer vaccine components in lymph nodes could contribute to new cancer vaccines that efficiently generate large populations of tumor-specific memory cells that control and cure pediatric cancers such as neuroblastoma.
Jeffrey Bednarski, MD/PhD, Washington University, St. Louis, MO
DNA Damage Responses Coordinate Survival and Cell Death Switching In Lymphocytes
During their development, immune cells must intentionally generate and repair breaks in their DNA in order to assemble the genes necessary for a diverse immune response. Multiple signals in early immune cells cooperate to ensure that these DNA breaks are properly repaired. Errors in these processes can derail normal development and trigger transformation into leukemia. Our research studies how immune cells respond to the DNA breaks in order to support correct repair and minimize the chances of deleterious events that could generate malignancies. Recent work has demonstrated that the DNA breaks themselves activate distinct pathways to first support cell survival and then subsequently trigger cell death mechanisms. This temporal sequence of survival and cell death allows time for DNA break repair but triggers elimination of cells with persistent DNA damage, which are at risk for errors that could initiate leukemia formation. How cells coordinate this balanced signaling is unknown. Interestingly, though, these signals are unique to physiologic DNA breaks, those encountered in normal development, as DNA damage from radiation or chemotherapy agents activate alternative pathways that trigger cell death rather than survival. The goal of this project is to understand how survival and cell death signaling is controlled in response to DNA breaks. Ultimately, these studies will identify new mechanisms in immune cells that ensure normal maturation and inhibit cancerous transformation. Understanding these processes will provide insights into the development and treatment of leukemia and lymphoma.
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’s sarcoma, glioma, leukemia, lymphoma, medulloblastoma, neuroblastoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma and Wilm’s tumor. In the United States, childhood cancer is the leading cause of death by disease in children under the age of 15. 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 $65 million toward fulfilling Alex’s dream of finding a cure, funding over 375 pediatric cancer research projects nationally. For more information on Alex’s Lemonade Stand Foundation, visit AlexsLemonade.org.