Progress for Relapsed Neuroblastoma: PHASE ONE Funds Breakthrough Study Using Enhanced Immune Cells
PHASE ONE Foundation has awarded a $400,000 Medical Grant to Dr. Araz Marachelian, Medical Director, Neuroblastoma MIBG Program at Children’s Hospital Los Angeles (CHLA) to support a Phase II clinical trial testing a powerful new treatment approach for children with relapsed or refractory high-risk neuroblastoma.
Neuroblastoma is the most common solid tumor outside the brain in children, and approximately half of all patients are diagnosed with high-risk disease—an aggressive form that is often widespread at the time of diagnosis. Even after enduring some of the most intensive treatments in pediatric oncology, only about 50% of children with high-risk neuroblastoma survive.
When the disease returns, response rates drop sharply and survival remains dismal, leaving families without a curative standard of care.
Over the last decade, one therapy has provided meaningful progress: dinutuximab, an immunotherapy that targets GD2, a protein found on neuroblastoma cells. When dinutuximab was added to standard treatment, event-free survival improved and it became the first FDA-approved immunotherapy for neuroblastoma, demonstrating that immunotherapy can work in pediatric solid tumors. Yet many children still relapse— not because immunotherapy is ineffective, but because neuroblastoma uses mechanisms like TGF-beta to suppress immune cells and evade destruction.
Dr. Marachelian’s research team is advancing a promising solution: strengthening immunotherapy by adding allogeneic Natural Killer (NK) cells that are enhanced in the laboratory and cryopreserved so they are ready when a patient needs treatment. NK cells are innate immune cells whose natural role is to recognize and destroy abnormal or stressed cells.
In a prior study by the New Approaches to Neuroblastoma Therapy Consortium (NANT), NK cells were collected from the patient, expanded in the lab, and infused after dinutuximab; the approach established dosing and showed a favorable safety profile, but patient-derived NK cells were limited in number, slower to manufacture, and often suboptimal in function.
The new Phase II trial addresses these barriers by using NK cells from carefully selected healthy universal donors with immune features linked to strong NK activity— an “optimal” profile present in about 6% of the population. For this study, such donors have already been identified, and their NK cells collected, expanded, and cryopreserved for off-the-shelf use.
In the laboratory, the NK cells are expanded in the presence of TGF-beta— an inhibitory molecule that normally prevents the immune system of neuroblastoma patients from effectively killing tumor cells. By exposing the donor NK cells to this suppressive environment during manufacturing, the team produces NK cells that become even better killers of neuroblastoma once infused.
Children in the trial will receive standard chemoimmunotherapy with dinutuximab along with these enhanced universal donor NK cells. The treatment can be given across multiple cycles because the NK cells are manufactured in advance and ready when needed— overcoming the production delays that were a challenge in previous trials. The primary goal is to improve the response rate for children whose cancer has returned after initial therapy.
“I’m deeply committed to advancing progress in relapsed neuroblastoma, and I’m grateful for this support. It allows us to move forward a promising idea – strengthening immunotherapy with donated NK immune cells – so we can work toward options for children who face relapse.” – Dr. Araz Marachelian, Principal Investigator
Six patients have already been enrolled and received therapy, including the NK cell infusions. All tolerated treatment well, and early experience has shown that children receiving this therapy have been able to continue normal daily activities, including attending school.
The trial aims to enroll 50 patients through the NANT Consortium, a national collaborative network dedicated to rapidly translating laboratory discoveries into clinical studies for relapsed neuroblastoma.
“For families facing aggressive cancers like relapsed high-risk neuroblastoma early-phase research is not abstract science, it’s a lifeline. Our job at PHASE ONE is to help turn that lifeline into a viable treatment option. We are honored to support this trial and look forward to its progress.” –Dr. Amanda Salvado, PHASE ONE Granting Co-Chair
If successful, this study could redefine how relapsed neuroblastoma is treated by pairing standard therapy with immune cells engineered to resist suppression and continue fighting. Findings from this study are expected to inform future immunotherapy approaches not only for neuroblastoma, but also for other pediatric cancers, helping accelerate development of new treatment strategies.