Differential killing of pre-B acute lymphoblastic leukaemia cells by activated NK cells and the NK-92 ci cell line

Abstract

The use of NK cells in adoptive therapy for malignant disease is an area of great potential. Currently the only NK cell line in clinical trials is NK-92, an activated NK cell line with a broad range of cytotoxicity against malignant cells. The activity of NK-92 against pre-B acute lymphoblastic leukaemias, however, is highly variable. In this study we compare the cytotoxic mechanisms and signalling pathways utilized by NK-92 ci and IL-2 activated NK cells to mediate killing of pre-B acute lymphoblastic leukaemia cell lines. Deficiencies in TNF family mediated apoptosis, phosphoinositide-3 kinase dependent and phosphoinositide-3 kinase independent killing limit the efficiency of NK-92 ci against pre-B acute lymphoblastic leukaemia cells. Importantly, treatment of the poorly killed leukaemia cells with TNF-alpha augmented both phosphoinositide-dependent and -independent cytolysis.