Details

Autor(en) / Beteiligte

• Knorr, David A.
• Ni, Zhenya
• Hermanson, David
• Hexum, Melinda K.
• Bendzick, Laura
• Cooper, Laurence J.N.
• Lee, Dean A.
• Kaufman, Dan S.

Titel

Clinical‐Scale Derivation of Natural Killer Cells From Human Pluripotent Stem Cells for Cancer Therapy

Ist Teil von

• Stem cells translational medicine, 2013-04, Vol.2 (4), p.274-283

Ort / Verlag

United States: AlphaMed Press

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Wiley Online Library Journals

Beschreibungen/Notizen

• This study used a two‐stage culture system to efficiently produce natural killer (NK) cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) in the absence of cell sorting and without need for xenogeneic stromal cells. Although different hESC and iPSC lines had varying efficiencies in hematopoietic development, all cell lines tested could produce functional NK cells. This improved method to develop NK cells from human pluripotent stem cells provides a system for clinical‐scale expansion of antitumor lymphocytes and a genetically amenable platform to study human NK cell development. Adoptive transfer of antitumor lymphocytes has gained intense interest in the field of cancer therapeutics over the past two decades. Human natural killer (NK) cells are a promising source of lymphocytes for anticancer immunotherapy. NK cells are part of the innate immune system and exhibit potent antitumor activity without need for human leukocyte antigen matching and without prior antigen exposure. Moreover, the derivation of NK cells from pluripotent stem cells could provide an unlimited source of lymphocytes for off‐the‐shelf therapy. To date, most studies on hematopoietic cell development from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have used incompletely defined conditions and been on a limited scale. Here, we have used a two‐stage culture system to efficiently produce NK cells from hESCs and iPSCs in the absence of cell sorting and without need for xenogeneic stromal cells. This novel combination of embryoid body formation using defined conditions and membrane‐bound interleukin 21‐expressing artificial antigen‐presenting cells allows production of mature and functional NK cells from several different hESC and iPSC lines. Although different hESC and iPSC lines had varying efficiencies in hematopoietic development, all cell lines tested could produce functional NK cells. These methods can be used to generate enough cytotoxic NK cells to treat a single patient from fewer than 250,000 input hESCs/iPSCs. Additionally, this strategy provides a genetically amenable platform to study normal NK cell development and education in vitro.