NANT2101 STING (Sequential Temozolomide, Irinotecan, NK cells, and GD2 mAb)​

Summary:

Neuroblastoma is the most common cancer diagnosed in infants. The average age of children when they are diagnosed is about 1 to 2 years and about 90% of cases are diagnosed by age 5.​ Historically treatment for patients with relapsed/refractory high-risk neuroblastoma was limited to chemotherapy (temozolomide and irinotecan) and about 17% of children responded to therapy.​ Current treatment for children with relapsed/refractory high-risk neuroblastoma includes immunotherapy (dinutuximab, a GD2 targeting monoclonal antibody) with the chemotherapy backbone and about half of patients respond to this treatment. ​Novel therapeutic approaches are desperately needed to improve outcomes in this rare population. ​One novel approach suggested by the investigators is the addition of natural killer (NK) cells to the standard chemoimmunotherapy regimen. ​NK cells play a pivotal role in anti-cancer immunosurveillance, and previous studies have found that NK cells are decreased in number and function in high-risk neuroblastoma. ​A lab at Nationwide Children’s Hospital has developed a novel ex-vivo expansion method for Universal Donor NK cells. Preclinical studies have demonstrated that they expanded NK cells to work synergistically with an anti-GD2 monoclonal antibody to kill neuroblastoma cells. ​Furthermore, the NK cells have been developed to overcome the immunosuppressive tumor microenvironment by chronically stimulating the NK cells with TGF-beta during the expansion process. TGF-beta is secreted by tumor cells and is responsible for suppressing NK cell function and other immune cells.​ This phase II study will assess the overall response rate of Universal Donor TGF-beta “imprinted” NK cells with chemoimmunotherapy in patients with relapsed/refractory high-risk neuroblastoma.

Trial Registration: ClinicalTrials.gov Identifier: NCT06450041