Children’s Hospital of Philadelphia Receives $1 Million Grant from Pediatric Cancer Foundation

Children’s Hospital of Philadelphia (CHOP) announced today it has received $1 million from Pediatric Cancer Foundation, an organization that has been raising funds for research since 1970 to support doctors and hospitals in an effort to eradicate childhood cancer. The grant will help to fund a planned first-in-human phase 1 clinical trial led by Sarah K. Tasian, MD, which will use a new immunotherapy to target the FLT3 receptor protein in high-risk pediatric leukemias.

Chemotherapy fails many patients with high-risk leukemias, particularly infants with acute lymphoblastic leukemia (ALL) and children with acute myeloid leukemia (AML) with high-risk genetic alterations who have poor long-term survival. Recent CAR T-cell therapies targeting the CD19 protein on ALL cells have been very effective in overcoming chemotherapy resistance and can now cure many children with relapsed ALL. However, some leukemias have learned to outsmart these therapies in various ways. One problem is that infant and childhood ALL with KMT2A genetic rearrangements are more likely to change into AML after CD19 CAR T-cell immunotherapy, which usually makes them incurable.

To date, it has been challenging to develop successful immunotherapies for pediatric AML. To address this problem, CHOP’s collaborative research team, led by Dr. Tasian and her colleague Dr. Terry Fry at Children’s Hospital Colorado, developed and tested a new CAR T-cell immunotherapy targeting an alternative protein called FLT3 that occurs at high levels in a type of AML and in infant ALL. In the laboratory, FLT3 CAR T cells were very effective at attacking and killing both AML and ALL cells in both in vitro and in vivo models of the disease. Remarkably, FLT3 CAR T cells eradicated both KMT2A-rearragned ALL and ALL that had turned into fatal AML after CD19 CAR T-cell treatment of the patient.

“Based upon our promising lab results, we aim to test FLT3 CAR T cells in pediatric patients through a first-in-human/child phase 1 clinical trial,” said Sarah K. Tasian, MD, a pediatric oncologist and Chief of the Hematologic Malignancies Program at CHOP. “Our research team has a strong track record of bench-to-bedside translation of CAR T cells for high-risk pediatric leukemias and is uniquely poised to undertake this challenge. Because of the funding provided by Pediatric Cancer Foundation, we can now work to translate our FLT3 CAR T-cell immunotherapy from promising results in the laboratory to the clinic. We hope that this clinical trial will have significant potential to credential a promising new immunotherapy against a shared target in two major types of high-risk childhood leukemias.”

“For the past decade, CHOP has been a recognized leader in the development of CAR-T cell therapy for use in pediatric cancers,” said Cheryl Rosen, Medical Liaison of Pediatric Cancer Foundation. “Pediatric Cancer Foundation is proud to partner with Dr. Sarah Tasian and CHOP to enable these promising laboratory results for treating both AML and ALL to be tested in a clinical trial. We hope that, together, we can significantly improve the survival rates of infants and children battling these cancers.”

The Cancer Immunotherapy Program at CHOP has revolutionized the care and the cure of children with relapsed/refractory B-cell ALL via its pioneering investigation of CD19-targeted killer T cells (CART19) that led to first-in-child FDA approval of the tisagenlecleucel cell therapy product in 2017. The program has continued to change and set new paradigms through investigation of additional CAR T cell therapies for children with B-cell ALL or lymphoma, AML, T-ALL, and neuroblastoma.

To find out more information visit, chop.edu/centers-programs/cancer-immunotherapy-program.