TY  - JOUR
A1  - Oberoi, Pranav
A1  - Kamenjarin, Kathrina
A1  - Villena Ossa, Jose Francisco
A1  - Uherek, Barbara
A1  - Bönig, Halvard-Björn
A1  - Wels, Winfried
T1  - Directed differentiation of mobilized hematopoietic stem and progenitor cells into functional NK cells with enhanced antitumor activity
T2  - Cells
N2  - Obtaining sufficient numbers of functional natural killer (NK) cells is crucial for the success of NK-cell-based adoptive immunotherapies. While expansion from peripheral blood (PB) is the current method of choice, ex vivo generation of NK cells from hematopoietic stem and progenitor cells (HSCs) may constitute an attractive alternative. Thereby, HSCs mobilized into peripheral blood (PB-CD34+) represent a valuable starting material, but the rather poor and donor-dependent differentiation of isolated PB-CD34+ cells into NK cells observed in earlier studies still represents a major hurdle. Here, we report a refined approach based on ex vivo culture of PB-CD34+ cells with optimized cytokine cocktails that reliably generates functionally mature NK cells, as assessed by analyzing NK-cell-associated surface markers and cytotoxicity. To further enhance NK cell expansion, we generated K562 feeder cells co-expressing 4-1BB ligand and membrane-anchored IL-15 and IL-21. Co-culture of PB-derived NK cells and NK cells that were ex-vivo-differentiated from HSCs with these feeder cells dramatically improved NK cell expansion, and fully compensated for donor-to-donor variability observed during only cytokine-based propagation. Our findings suggest mobilized PB-CD34+ cells expanded and differentiated according to this two-step protocol as a promising source for the generation of allogeneic NK cells for adoptive cancer immunotherapy.
KW  - natural killer cells
KW  - hematopoietic stem and progenitor cells
KW  - feeder cells
KW  - natural cytotoxicity
KW  - adoptive cancer immunotherapy
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53424
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-534245
SN  - 2073-4409
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 9
IS  - 811
PB  - MDPI
CY  - Basel
ER  -