Combinatorial Immunotherapy of N-803 (IL-15 Superagonist) and Dinutuximab with Ex Vivo Expanded Natural Killer Cells Significantly Enhances in Vitro Cytotoxicity against GD2
Journal for Immunotherapy of Cancer
Health Behavior and Community Health
BACKGROUND: Children with recurrent and/or metastatic osteosarcoma (OS), neuroblastoma (NB) and glioblastoma multiforme (GBM) have a dismal event-free survival (
METHODS: The anti-tumor combinatorial effects of N-803, dinutuximab and ex vivo expanded peripheral blood NK cells (exPBNK) were performed in vitro using cytoxicity assays against GD2
RESULTS: N-803 increased the viability and proliferation of exPBNK. The increased viability and proliferation are associated with increased phosphorylation of Stat3, Stat5, AKT, p38MAPK and the expression of NK activating receptors. The combination of dinutuximab and N-803 significantly enhanced in vitro cytotoxicity of exPBNK with enhanced perforin and IFN-γ release against OS, GBM and NB. The combination of exPBNK+N-803+dinutuximab significantly reduced the secretion of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), platelet-derived growth factor-BB (PDGF-BB), and stem cell growth factor beta (SCGF-β) from OS or GBM tumor cells. Furthermore, OS or GBM significantly inhibited the secretion of regulated on activation, normal T cell expressed and presumably secreted (RANTES) and stromal cell-derived factor-1 alpha (SDF-1α) from exPBNK cells (p
CONCLUSIONS: Our results provide the rationale for the development of a clinical trial of N-803 in combination with dinutuximab and ex vivo exPBNK cells in patients with recurrent or metastatic GD2+ solid tumors.
Chu, Y., Nayyar, G., Jiang, S., Rosenblum, J. M., Soon-Shiong, P., Safrit, J. T., Lee, D. A., & Cairo, M. S. (2021). Combinatorial Immunotherapy of N-803 (IL-15 Superagonist) and Dinutuximab with Ex Vivo Expanded Natural Killer Cells Significantly Enhances in Vitro Cytotoxicity against GD2. Journal for Immunotherapy of Cancer, 9 (7), e002267-e002267. https://doi.org/10.1136/jitc-2020-002267