Accelerated human hematopoeitic stem cell differentiation towards mature natural killer cells with enhanced antibody-dependent cytotoxic activity
AssigneeUniversiteit Gent
InventorsLaura Kiekens, Georges Leclercq
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Abstract
The present invention in general relates to a method of differentiating human hematopoietic stem cells (HSC) into mature natural killer (NK) cells; wherein said method is in particular characterized in that mature NK cells are obtainable very early during the differentiation method, and that these NK cells display increased CD16 expression and antibody-dependent cellular cytotoxicity (ADCC) (FIG. 11). The method of the invention specifically encompasses transfecting and/or transducing HSCs with at least one transcription factor selected from T-Box expressed in T cells (T-BET) and Eomesodermin (EOMES); or a combination thereof.
Claims16
A method of differentiating hematopoietic stem cells (HSC) into mature natural killer (NK) cells, said method comprising the steps of:
- a) providing isolated HSCs;
- b) culturing said cells of step a) in medium containing thrombopoietin (TPO), stem cell factor (SCF) and FMS-like tyrosine kinase 3 ligand (FLT3-L);
- c) transfecting and/or transducing said cells of step b) with at least one transcription factor selected from the list comprising:
- T-Box expressed in T cells (T-BET) or Eomesodermin (EOMES);
- or a combination thereof;
- d) culturing the cells obtained from step c) in a medium containing at least one cytokine selected from the list comprising IL-2 or IL-15;
- preferably IL-15;
- whereby said mature NK cells are obtainable from day 3 after the start of step d).
A hematopoietic stem cell (HSC) transfected and/or transduced with T-Box expressed in T cells (T-BET), Eomesodermin (EOMES), or a combination of Eomesodermin (EOMES) and T-Box expressed in T cells (T-BET).
Dependencies are inferred from the claim text.