发明名称 |
EX VIVO NK CELL DIFFERENTIATION FROM CD34+ HEMATOPOIETIC CELLS |
摘要 |
The present invention relates to the ex vivo differentiation of NK cells from CD34+ hematopoietic stem cells. Such NK cells and their progenitor cells can be used in therapies of a broad range of malignancies. In the present invention it is shown that IL-12 modulates ex vivo NK cell differentiation. Specific, we achieved significantly higher expression of KIR, CD16 and CD62L in the presence of IL-12 in the cell culture system. The induction of receptor expression by IL-12 occurred predominantly on an augmented population of CD33+NKG2A+ NK cells early during NK cell differentiation. These cells further show enhanced cytolytic activity against MHC class I positive AML targets. In line with the enhanced CD16 expression, IL-12 modulated ex vivo generated NK cells exhibit an improved antibody-dependent-cytotoxicity, using anti CD20 antibody on various B cell targets. Additional to the enhanced expression of CD62L, we show that this cell population consists of a specific chemokine receptor profile. By showing an increased capacity for adhesion to lymphendothelial cells and a specific chemokine receptor profile, we show that IL-12 provided the ex vivo generated NK cells with specific tissue-homing abilities. |
申请公布号 |
US2015010583(A1) |
申请公布日期 |
2015.01.08 |
申请号 |
US201314376870 |
申请日期 |
2013.02.07 |
申请人 |
Spanholtz Jan |
发明人 |
Spanholtz Jan |
分类号 |
C12N5/0783;A61K35/14;A61K39/395 |
主分类号 |
C12N5/0783 |
代理机构 |
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代理人 |
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主权项 |
1. A method for producing NK cells said method comprising
i—providing a sample of human CD34 positive cells, ii—expanding said CD34 positive cells ex vivo, iii—culturing CD34 positive cells obtained in step ii ex vivo in an NK-cell differentiation medium, said method characterized in that said NK-differentiation medium comprises IL-12. |
地址 |
Kleve DE |