Intracellular delivery of synthetic dsRNA to leukemic cells induces apoptotic and necrotic cell death

Abstract

The type of tumour cell death dictates the type of adaptive immune response mounted against the tumours. In haematological malignancies such as acute myeloid leukaemia (AML), immune evasion due to the poor immunogenicity of leukemic cells is a major hurdle in generating an effective immune response. Transfection of synthetic dsRNA, poly I:C, into leukemic cells to trigger tumour cell death and enhance immunogenicity of the tumour is a promising immunotherapeutic approach. However, the temporal cell death kinetics of poly I:C-electroporated AML cells has not been thoroughly investigated. Electroporation of U937 cells, a human AML cell line, with a high dose of poly I:C resulted in cytotoxicity as early as 1 h post-transfection. Flow cytometric analysis revealed the temporal switch from early apoptosis to late apoptosis/secondary necrosis in poly I:C-electroporated cells in which the nuclear morphology at later time points was consistent with necrotic cell death. Our brief findings demonstrated the temporal cell death kinetics of dsRNA-transfected leukemic cells. This finding is an important development in the field of dsRNA immunotherapy for leukaemia as understanding the type of cell death elicited by transfected dsRNA will dictate the type of immune response to be directed against leukemic cells.