Neuroblastoma developmental therapeutics research and discoveries
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Our history in neuroblastoma breakthroughs
At Children’s Hospital of Philadelphia (CHOP), there is a rich history of neuroblastoma clinical care, research and innovation ever since Dr. Audrey Evans was recruited in 1969 to be the inaugural Chief of the Division of Oncology. Working with Dr. Dan D’Angio, she created the first “staging” system that allowed physicians to more precisely choose therapy, and they provided the first description of the enigmatic “4S” neuroblastoma that spontaneously goes away without therapy.
Drs. Evans and D’Angio inspired generations of doctors, scientists, nurses, social workers and other healthcare professionals, including each of the current members of the NBDT team. John M. Maris, MD, started the NBDT program in 1999 when he opened a clinical trial of the targeted radiotherapeutic 131I-MIBG. For two decades, CHOP and the NBDT team have been leaders in the New Approaches to Neuroblastoma Therapy Consortium. Yael P. Mossé, MD, brought innovative precision medicine therapies to the team over the last 15 years and leads the NBDT program with Dr. Maris. Most recently, two chimeric antigen receptor (CAR) T-cell therapies have been created in NBDT team labs that are currently open for enrollment in “first-in-human / first-in-child” clinical trials with other immunotherapies in development.
Paradigm-shifting contributions
NBDT investigators have continuously made paradigm-shifting contributions to our understanding of neuroblastoma biology with a translational focus.
- We have played a pivotal role in the establishment of our current standards of care, and we have leadership roles in the implementation of these trials through the Children’s Oncology Group (COG).
- We have led the efforts to develop the portfolio of nonclinical and clinical data required to test the efficacy of the targeted radiotherapeutic 131I-MIBG and ALK inhibition therapy in the COG ANBL1531 Phase 3 clinical trial.
- We have led the development of precision oral medications for patients whose tumors have an ALK mutation at any time throughout their therapy, in children and adults, and in families where neuroblastoma is inherited.
- We also seek to repurpose adult cancer medications for other mutations we discover during our care.
- We developed a neuroblastoma-specific “liquid biopsy” available at CHOP to find new mutations and to monitor for a “molecular” remission.
The laboratory and NBDT teams are currently working on multiple classes of new therapies including, but not limited to:
- Next-generation CAR T-cell therapies
- Antibody drug conjugate therapies
- Precision small molecular therapies
- Vaccines for prevention of relapse
- Vaccines to “boost” CAR T-cell therapies
- Protein degrader therapies
- “Synthetic lethal” therapies
- Targeted radiotherapies (MABG)
Each of these classes of drugs are created in the NBDT physician-scientist laboratories based on observations from human neuroblastoma samples with the goal creating safe and effective new therapies for patients with high-risk neuroblastoma and other childhood cancers.
Development of new lab tests
The NBDT team has also created new lab tests, several of which have been incorporated into helping to determine how much and which treatment patients with newly diagnosed neuroblastoma should receive.
More recently, the NBDT team developed a neuroblastoma-specific “liquid biopsy” (circulating tumor DNA) assay in collaboration with the CHOP Division of Genomic Diagnostics for patients and ordering physicians internationally. This test was designed to be much more “sensitive” than assays commonly used primarily for adult cancers, meaning we can detect a relapse well before it would be detected on standard scans or bone marrow tests.
Additionally, we have learned that mutations in potentially druggable genes like ALK can emerge at any time during therapy, which makes this liquid biopsy test a tool available for any neuroblastoma patients across the treatment course and after.
To order these labs:
Clinical trials
Clinical trials are research studies that test new medical approaches, like drugs or therapies, in people to see if they are safe and effective.
These are currently open clinical trials derived from our research programs:
- PHOX2B PC-CAR T Cells for Relapsed Neuroblastoma (PHOX2B)
- GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma
- I-MIBG Therapy for Refractory Neuroblastoma: Expanded Access Protocol
- NANT.org
For more available clinical trials, please visit ClinicalTrials.gov.
Our current research
The co-leads of the NBDT program, John Maris, MD, and Yael P. Mossé, MD, have laboratories that are relentlessly focused on neuroblastoma. They conduct ongoing, cutting-edge investigations into the molecular and genetic mechanisms contributing to this disease, with the goal of developing biomarker-directed precision therapeutics.