B+ Research Grants

A sampling of Research Grants Funded by The B+ Foundation
Dana-Farber cancer institute

Zebrafish Models of Human AML

Dana-Farber/Harvard Medical Center, Boston, MA

Zebrafish present an exciting way to cost-effectively accelerate the learning of drug development effectiveness.  The B+ Foundation is proud to have provided multiple research grants to Dr. Evisa Gjini in Dr. Thomas Look’s lab at Dana-Farber/Harvard Medical Center.

 

Children's Oncology Group

BioStatistician

Children’s Oncology Group, Monrovia, CA

With advancements in technology, data is often getting ahead of our human capacity to manage it, parse it, and share it.  It does us no good to have mountains of data that is out of the reach of the researchers.  For that reason, The B+ Foundation has funded a Masters level biostatistician at the COG.  This investment will not only help one researcher but, potentially, dozens as critical data is shared with numerous investigators.

 

 

Project EveryChild

The Children’s Oncology Group, Philadelphia, PA

 

The Children’s Oncology Group (COG) is the preeminent body who oversees non-governmental research funded by the National Cancer Institute (NCI).  The COG is made up of institutions in North America, Australia, New Zealand, and part of Europe.  Ninety percent of children treated for cancer in the United States are treated at COG hospitals.  The COG is led by internationally known pediatric oncologist, Dr. Peter Adamson of the Children’s Hospital of Philadelphia (CHOP).

Dr. Adamson has been a great supporter of The B+ Foundation and we are proud to support a long-overdue initiative in Project EveryChild.

This project strives to capture tissue/blood/tumor samples from every pediatric cancer patient in the country and store them in a bio-repository in Columbus, OH.  By gathering this information, we can significantly assist researchers as they require ample samples of these “rare” childhood cancers.

Project EveryChild will likely have a profound effect on childhood cancer research and, like ALL of the other research that we fund, it will benefit the entire childhood cancer community as collaboration is a requirement of ours.

 

Project: Everychild
B+ Heroes
Therapy Architects

“ALL” Drug Development

Therapy Architects, Wilmington, DE

The B+ Foundation has provided assistance in the early-stage development process of a novel treatment of Acute Lymphocytic Leukemia (“ALL”) being evaluated by Therapy Architects.

MD Anderson Cancer Center

Pediatric Colon Cancer Phase I Clinical Trial

MD Anderson, Houston, TX

Under the direction of Dr. Andrea Hayes-Jordan, The B+ Foundation is proud to support the Phase I Trial of Oxaliplatin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Children and Adolescents with Extensive Colon Carcinoma.

Nemours

Phase II Ewing’s Sarcoma Clinical Trial

Nemours/A.I. DuPont Hospital, Wilmington, DE

The B+ Foundation supported Dr. Andy Kolb’s work on the Phase II Ewing’s Sarcoma Clinical Trial in conjunction with the COG Bone Sarcoma Disease Committee.

Pediatric Cancer Genome Project

St. Jude Children’s Research Hospital, Memphis, TN

St. Jude Children’s Research Hospital, in collaboration with Washington University of St. Louis, are engaged in an unprecedented effort to identify the genetic changes that give rise to some of the world’s deadliest childhood cancers. The team has joined forces to decode the genomes of more than 600 childhood cancer patients.

The St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project is the largest investment to date aimed at understanding the genetic origins of childhood cancers. Scientists involved in the project are sequencing the entire genomes of both normal and cancer cells from each patient, comparing differences in the DNA to identify genetic mistakes that lead to cancer.

The investment in the overall project exceeds $50,000,000.  The B+ Foundation is proud to support Dr. Tanja Gruber’s work in this very worthwhile project.  The Pediatric Cancer Genome Project will yield valuable information that will be the foundation of childhood cancer research for decades.

St. Jude Children's Research Hospital
Van Andel Institute

Preclinical Development of Survivin Inhibitor in Pediatric Cancer

Van Andel Research Institute, Grand Rapids, MI

Dr. Giselle Sholler has received financial support from The Andrew McDonough B+ Foundation to support her cutting-edge research on Neuroblastoma.

The goal of this research is to bring forward the preclinical work needed to test the survivin inhibitor YM155 in Neuroblastoma and pediatric solid tumors. This novel pathway is critical in tumor growth and important to explore in pediatric cancer.

Given the lack of effective therapeutic options for relapsed/refractory NB this is potentially an important trial that may have significant therapeutic impact for affected children.

Cincinnati Children's Hospital

‘Eyes Absent’ Gene Investigation in Ewing’s Sarcoma Patients

Cincinnati Children’s Hospital, Cincinnati, OH

Based on laboratory investigation at Cincinnati Children’s Hospital, researchers have found that a gene called ‘Eyes Absent’ (EYA) plays a critical role in Ewing’s sarcoma and, more importantly, may provide a promising new target for treating Ewing’s sarcoma patients. Dr. Hegde, with the support of Drs. Pressey and Szabo, intend to determine the role of EYA in tumor growth, spread, and resistance to conventional chemotherapy. They will also study promising new agents that inhibit the function of EYA.

Ultimately, they anticipate that their findings may shed light on the biology underlying Ewing’s sarcoma and translate into the discovery of improved treatments for Ewing’s sarcoma and other cancers. This project will pair Cincinnati Children’s Hospital’s pediatric oncology sarcoma physicians with expert pathologists and world class laboratory scientists, offering hope to the many Ewing’s sarcoma patients that are diagnosed each year.

 

UIC

Trial Manager for Clinical Trials for Lower Income Patients

University of Illinois-Chicago (UIC), Chicago, IL

Sadly, children at UIC were not getting the same clinical trial opportunities as patients at other institutions.  UIC treats many lower income families and, in combination with two other local institutions (Rush, Stroger), Dr. Mary Lou Schmidt created an opportunity to significantly impact this situation.  The B+ Foundation stepped in and funded the Trial Manager’s salary so that this project could come to fruition.

Nemours

High Throughput Screening Device

Nemours/A.I. DuPont Hospital, Wilmington, DE

A high throughput screening (HTS) device is a costly piece of equipment that can significantly accelerate the drug development process.  The HTS can accomplish in a few days what would take bench scientists years to do.  The potential and impact of this piece of equipment is far-reaching and being shared well beyond this one institution.

Phase I Clinical Study of CT Antigen Vaccine and Decitabine for Patients with Relapsed Neuroblastoma

University of Louisville, Louisville, KY

The B+ Foundation was pleased to partner with another childhood cancer charity, Solving Kids Cancer (New York City) to co-fund this exciting work being done by Dr. Ken Lucas.  The work, initially started at Penn State/Hershey Hospital and Dana-Farber, is now being carried out at the University of Louisville.

The most promising aspect of this trial is the utilization of a combination of novel agents at the forefront of cancer research for a poor?prognosis type of pediatric cancer. This particular clinical study builds on four years of research in vaccine therapeutic strategies for pediatric cancers and this may well impact the treatment paradigm for Neuroblastoma. This trial provides significant potential for efficacy as it uses a personalized vaccine in combination with a novel chemotherapeutic agent given in repeated cycles. Pre?clinical studies confirmed that decitabine upregulates the specific antigens that the vaccine targets on the tumor cells.

Early results have been very promising with a child with a very poor prognosis now in complete remission.

University of Louisville
rockefeller

 

Tumorigenesis of a Pediatric Liver Cancer

The Rockefeller University, New York, NY

Many cancers are the consequence of a change in activity of a particular kind of protein called a kinase.  A kinase works by modifying other proteins by adding on to them a particular compound called a phosphate. In some cancers there is an increase in the amount of the kinase that is made; in other cancers the kinase is trapped in the “on” position and is not properly regulated by the cell. Drug therapies that inhibit kinases that add phosphates to proteins on the amino acid tyrosine, have already been approved by the FDA for treatment of non-small cell lung cancer, renal cell carcinoma, chronic myelogenous leukemia (CML), human epidermal growth factor (Her2+) breast cancer, myelofibrosis, gastrointestinal stromal tumor (GIST), and melanoma.  While there are kinases that add phosphates to other amino acids, they have not been studied as potential drivers of cancer. We are studying a specific pediatric cancer that forms in the liver, fibrolamellar hepatocellular carcinoma (FLHCC). We discovered that the only alteration in the tumor cells is the formation of a variant of a kinase which adds phosphates onto the amino acids serine or threonine.

We want to understand how such a kinase can cause cancer.  If we know how it is working, then we are in a better position to block it without affecting the normal functioning of the cells.  With support of the B+ Foundation we are developing the technology for studying the changes that result from an altered kinase in the cell.  This will provide both better understanding of fibrolamellar, provide targets for treatment the disease, but also develop a new way to study the many cancers that are the consequence of an altered kinase in the cell.

 

 

DUKE

 

Phase I Polio Oncolytic Virotherapy (PVS-RIPO) of Pediatric High-Grade Glioma

Duke University Medical Center, Durham, NC

The B+ Foundation is pleased to support this exciting new immunotherapy for children with deadly brain tumors conducted by Dr. Oren Becher at Duke University. Oncolytic viruses are capable of stimulating immune responses against tumor-associated antigens that can produce lasting immunologic control of cancers. 

PVS-RIPO is a polio-derived oncolytic virus engineered to selectively kill brain tumor cells, and has shown some dramatic responses without toxicity in adults with universally fatal recurrent glioblastoma. This has garnered the attention of the oncology research community and was highlighted by 60 minutes in March 2015, and now will be available to pediatric patients in mid-2016. This pediatric trial will enroll 10-15 children with recurrent high-grade gliomas, and the PVS-RIPO poliovirus is directed to the tumor by convection-enhanced delivery. The researchers will determine the optimum dose and any toxicities

There are promising therapies in adults that The B+ Foundation has worked hard to make available to children with deadly tumors  and no options. Given the promising results in adults, expectations are high this will be very effective in children as well.  Read more about the development of this oncolytic virus.

The B+ Foundation provided the essential support to this exciting work, summed up by oncologist Dr. Henry Friedman: “This, to me, is the most promising therapy I’ve seen in my career, period.”

 

Seattle

Immunotherapy may be the most exciting area of research in childhood cancer today.  In short, a patient’s T-cells are removed from their body, re-programmed to fight their particular type of cancer, and re-inserted into the body.  Immunotherapy could potentially replace chemotherapy for some patients, or at least reduce the use of side-effect-causing chemotherapy.

There are a few centers of excellence that are working on immunotherapy right now, and The B+ Foundation has provided multiple grants to Dr. Michael Jensen’s lab at the Ben Towne Center for Childhood Cancer Research at Seattle Children’s Hospital.  In the initial group of patients, the doctors are seeing survival rates for relapsed leukemia increasing from 15% to 91%!  Read the full article.

The B+ Foundation has purchased a Nuance Imaging System and a Droplet PCR machine for the lab.  Our contribution to this exciting work was described by a lead investigator as “game changing”!

University of Louisville

The genomics era was anticipated to bring with it the capacity to use molecular biology tools to identify specific cancer-causing mutations and translate that information into better therapy. For most children with cancer, especially diseases like rhabdomyosarcoma which harbors few identifiable mutations, this promise has not been fully realized. Researchers in the Skapek laboratory at UT Southwestern Medical Center have developed a new computational pipeline to identify candidate rhabdomyosarcoma “drivers” that foster tumor formation or progression. With funding from The Andrew McDonough B+ Foundation, the Skapek laboratory team is carrying out functional studies of the candidate drivers to validate the utility of the new analysis pipeline and identify those drivers that could represent new therapeutic targets for rhabdomyosarcoma.

university hospital

 

Genetic Patterns of Signet Ring Cell Colon Cancer

University Hospital, Cleveland, OH

Under the leadership of renowned colon cancer geneticist Dr. Sanford Markowitz, UH Seidman Cancer Center is currently executing an ambitious plan to study the genetic patterns of signet ring cell colon cancer. Because this disease is so rare, finding signet ring cell tumors and analyzing their genetic structure is a complex, time-consuming, and expensive process. The goal of this supported work is to secure additional signet cancer tumors that can be genetically sequenced and, if possible, grown in the lab.  Additionally, create mouse models of signet ring cancer that allow the team to identify the pathways these tumors require to be able to grow. This will also enable the team to test the ability of different anti-cancer drugs to target these pathways and to shrink or eliminate these types of tumors.

 

 

university hospital

 

Preclinical Development of Novel Immunotherapies for Pediatric Acute Myeloid Leukemia (AML)

Children’s Hospital of Philadelphia, Philadelphia, PA

Many children with acute myeloid leukemia (AML) are resistant to chemotherapy and/or will relapse. New treatments are needed to improve outcomes for these patients. We are testing new “killer T cell” immunotherapies in specialized pediatric AML mouse models with the goal of rapid translation into clinical trial testing for children with relapsed/refractory AML. We hypothesize that creation of an armamentarium of chimeric antigen receptor (CAR)-engineered T cell immunotherapies is necessary to improve cure rates substantially given the underlying biologic and genetic heterogeneity of childhood AML. Our first laboratory studies testing a new CAR T cell therapy in our AML mouse models have directly informed the development of two soon-to-open clinical trials at Penn and CHOP that will test the effectiveness of this immunotherapy in adults and children with relapsed AML.

 

 

Children's Oncology Group

 

TARGET Pediatric AML Initiative

Children’s Oncology Group

The TARGET Pediatric AML Initiative was identified by the Children’s Oncology Group acute myeloid leukemia (AML) leadership team as the highest potential and greatest need effort in our research portfolio to benefit children, adolescents and young adults fighting AML.  The goal of this initiative is to uncover the genetic drivers of AML in young people and maximize the use of both existing and emerging therapies, and accelerate the discovery new ones.

What is the TARGET Pediatric AML Initiative?

AML is also a highly complex, diverse group of diseases driven by multiple genetic mutations, some occurring in combinations that can be patient-specific. As such, “one size fits all” or single-agent therapeutic strategies may be less effective against this disease.  The goal of this initiative is to use the most advanced tools available to establish a rapid discovery platform and identify the right “targets” for new and existing drugs and therapies.  Developing a robust list of pediatric AML target mutations mapped to a “toolbox” of weapons (drugs & therapies) will be key.  These discoveries are the very foundation of personalized/precision medicine and are urgently needed in AML research to reduce treatment-related toxicities.

What needs to get done?

The Children’s Oncology Group will roll out this initiative in two phases.  Phase 1 will include deep genomic sequencing on patient samples, hiring computational staff to fully analyze data, testing and verification to determine if a target is in fact driving the cancer, and sequencing sick kids now for disease monitoring, early relapse detection, and treatment option discovery.  This will help us better understand why responders to therapy responded, while others did not.

Phase 2 of the initiative will entail expanding sequencing, analysis, and target discovery to a much larger patient population in order to generate a comprehensive list of targets and biomarkers for AML in young people.  This will allow us to design targeted, patient-specific treatments geared towards the patient’s specific cancer profile.