$5.5 Million

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Midhat Farooqi, M.D., Ph.D.
Director, Molecular Oncology
Children’s Mercy Genome Center

Targeting solid tumors with multi-antigen specific T cells by identifying the genetic and epigenetic determinants of therapeutic response

T cells, a type of immune cell, circulate in our bodies and scan for microbes as well as abnormal cells. In the laboratory, exposing T cells to small fragments of proteins (“antigens”) expressed on the surface of tumor cells trains these T cells to recognize cancer cells and eradicate them. This finding led to the recent development of ‘multi-antigen specific T cells’ (MAS T cells), a safe and novel form of targeted therapy for a range of pediatric solid tumors including neuroblastoma, Ewing Sarcoma and Wilms tumor. Dr. Farooqi’s team seeks to understand whether a tumor’s genetic profile affects its response to MAS T cell infusion. With funding from Braden’s Hope, his team is performing comprehensive genetic sequencing of patient tumor samples pre- and post-therapy. The project involves patients and tumor samples from Children’s National Medical Center in Washington, D.C.; Children’s Health in Dallas, Texas, and Cook Children’s in Fort Worth, Texas, with plans in the near future to include samples from the Instituto Nacional de Pediatria in Mexico City, Mexico.

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John M. Perry, Ph.D.
Research Faculty, Children’s Mercy Research Institute
Hematology/Oncology/BMT

Overcoming therapeutic resistance by repurposing a classic chemotherapeutic drug as a targeted therapy to reactivate anti-cancer immunity

Our immune systems normally recognize potentially cancerous cells early enough to prevent tumor development. However, cancer stem cells, which are resistant to most therapies and cause cancer relapse, are especially good at evading and resisting the immune system. Dr. Perry’s team found that a long-used chemotherapy drug, doxorubicin, could be used in a more targeted manner to stimulate the immune system and replenish normal stem cells, while inhibiting cancer stem cell’s immune evasion. Dr. Perry is now focused on developing a new drug, with similar properties as doxorubicin but with more potent and specific effects. With support from Braden’s Hope, Dr. Perry’s long-term goal is to eliminate cancer stem cells and provoke an immune response that will effectively vaccinate patients against relapse.

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Tomoo Iwakuma, M.D., Ph.D.
Director, Translational Laboratory Oncology Research Program, Children’s Research Institute
Volunteer faculty of Department of Cancer Biology, KUMC
Co-leader of Cancer Biology Program, KU Cancer Center

Capitalizing on p53 loss/mutations in osteosarcoma by novel compounds

Dr. Iwakuma’s team has identified a new compound that kills only cancer cells lacking a key cancer-preventive protein called “tumor suppressor p53.” Since over 50% of human cancers and specifically about 80% of osteosarcoma cases lose the p53 activity, and because normal tissues have intact p53 activity, Dr. Iwakuma’s compound has the potential to only kill cancer cells with minimal side effects to healthy cells. With support from Braden’s Hope, Dr. Iwakuma’s team recently discovered that this compound also blocks one of the key DNA damage repair machineries in cells that lose p53 activity and inhibits osteosarcoma tumor growth in mouse models. The team is modifying the chemical structure of this compound so that it can be suited for clinical use in pediatric patients. Dr. Iwakuma is quick to point out that without Braden’s Hope, his research would not have progressed as far as it has in less than three years.

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We funded a two-year, $200,000 study to Dr. Andrew Godwin and Dr. Glenson Samuel at KU Medical Center for Ewings Sarcoma research. The study is “Exosome miRNAs as biomarkers and targets for chemoresistance in Ewing Sarcoma”.

We also funded a two-year, $300,000 study to Dr. Shrikant Anant from KU Medical Center and Dr. Kathleen Chastain from Children’s Mercy Hospital for “Sarcoma in a Dish: a novel approach for precision medicine”. This study seeks to find answers for Rhabdomyosarcoma cancers in children.

We funded a third study which was a one-year $100,000 study to Dr. Yael Mosse, titled “Immunotherapeutic Strategies to Target ALK on the Cell Surface of High Risk Neuroblastoma”. This study addresses high risk neuroblastoma and is a precision medicine approach to treating this deadly disease.

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Two grants were awarded this year. One was to Dr. Kathleen Chastain from Children’s Mercy Hospital in conjunction with Dr. Shrikant Anant at KU Medical Center for rhabdomyosarcoma research. The amount of that grant was $193,700.

The second grant totaling $100,000 was awarded to Dr. Andrew Godwin from KU Medical Center in conjunction with Dr. Kathleen Chastain of Children’s Mercy Hospital for work in the area of Ewings Sarcoma.

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We awarded two grants in 2014. One was to Dr. Kathleen Neville at Children’s Mercy Hospital in conjunction with Dr. Giselle Sholler from Helen deVos Hospital in Grand Rapids, Michigan. This was a Phase One research trial with two targeted treatment drugs called DFMO and Velcade which are given to patients who have gone through neuroblastoma treatments in an attempt to keep them in remission as a high percentage of neuroblastoma patients relapse.

The second grant was awarded in 2014 was to Dr. Doug Myers from Children’s Mercy Hospital in partnership with Dr. Thomas Yankee at KU Medical Center. Their research focuses on all solid mass tumors and the grant title was Next generation chimeric antigen receptors for personalized anti-tumor therapy.  Their work focuses on infusing donor cells from a relative that are “supercharged” into a childhood cancer patient. Those cells then target cancer cells to destroy them and teach the child’s own immune system to recognize the invading cancer cells and destroy them. This is the second phase of their work and the preliminary results from the first phase of their work were extremely promising.

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Our first grant was awarded to Dr. Jason Shohet at Texas Children’s Hospital to find a specific stem cell that is believed to be an activator of neuroblastoma cancers. His work was designed to find that cell, learn what activates it, and then develop a treatment that would shut that cell activator down.