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- Title
Human CD80/IL2 lentivirus-transduced acute myeloid leukaemia (AML) cells promote natural killer (NK) cell activation and cytolytic activity: implications for a phase I clinical study.
- Authors
Ingram, Wendy; Chan, Lucas; Guven, Hayrettin; Darling, David; Kordasti, Shahram; Hardwick, Nicola; Barber, Linda; Mufti, Ghulam J.; Farzaneh, Farzin
- Abstract
Immunotherapeutic strategies may promote T and/or natural killer (NK) cell cytotoxicity. NK cells have the potential to exert a powerful anti-leukaemia effect, as demonstrated by studies of allogeneic transplantation. We have previously shown that CD80/interleukin 2 (IL2) lentivirus (LV)-transduced AML cells stimulate in-vitro T cell activation. The present study demonstrated that allogeneic and autologous culture of peripheral blood mononuclear cells with CD80/IL2-expressing AML cells also promoted NK cell cytotoxicity. Expression of the activation receptors NKp30, NKp44, CD244, CD25, CD69 and HLA-DR significantly increased following allogeneic culture and a consistent increased expression of NKp30, NKp44, NKp46, NKG2D, NKG2C and CD69, and up-regulation of the cytolytic marker CD107a was detected following autologous culture with LV-CD80/IL2 AML cells. Furthermore, increased NK cell lysis of K562 and primary AML blasts was detected. The lytic activity increased by twofold against K562 (from 46·6% to 90·4%) and allogeneic AML cells (from 11·8% to 20·1%) following in-vitro stimulation by CD80/IL2-expressing AML cells. More importantly for potential therapeutic applications, lysis of primary AML cells by autologous NK cells increased by more than 40-fold (from 0·4% to 22·5%). These studies demonstrated that vaccination of patients with CD80/IL2-transduced AML cells could provide a powerful strategy for T/NK cell-mediated stimulation of anti-leukaemic immunological responses.
- Subjects
ACUTE myeloid leukemia; LENTIVIRUSES; KILLER cells; CELL-mediated cytotoxicity; T cells
- Publication
British Journal of Haematology, 2009, Vol 145, Issue 6, p749
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2009.07684.x