Enhancement of anti-tumor activity of expanded natural killer cells against GD2+ osteosarcoma (OS) in combination with romidepsin (HDAC inhibitor), ALT-803 (IL-15 Superagonist) and dinutuximab

      Background: Children with recurrent and/or metastatic OS have dismal EFS (<25%). Dinutuximab is an anti-GD2 monoclonal antibody that has significantly increased EFS in children with GD2+ neuroblastoma (Yu AL, N Engl J Med , 2010). Romidepsin is a histone deacetylase inhibitor that increases the expression of NKG2D ligands in Burkitt Lymphoma (Chu/Cairo, et al., Cytotherapy, 2014). ALT-803 is a superagonist of an IL-15 variant bound to an IL-15RαSu-Fc fusion with enhanced biological activity (Zhu et al. 2009 J Immunol). Our group has successfully expanded peripheral blood Natural Killer cells (exPBNK) with irradiated feeder cells (Chu/Cairo, et al., Can Imm Res 2015).
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