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, 65 (4), 477-84

Selection and Expansion of Natural Killer Cells for NK Cell-Based Immunotherapy


Selection and Expansion of Natural Killer Cells for NK Cell-Based Immunotherapy

Petra S A Becker et al. Cancer Immunol Immunother.


Natural killer (NK) cells have been used in several clinical trials as adaptive immunotherapy. The low numbers of these cells in peripheral blood mononuclear cells (PBMC) have resulted in various approaches to preferentially expand primary NK cells from PBMC. While some clinical trials have used the addition of interleukin 2 (IL-2) to co-stimulate the expansion of purified NK cells from allogeneic donors, recent studies have shown promising results in achieving in vitro expansion of NK cells to large numbers for adoptive immunotherapy. NK cell expansion requires multiple cell signals for survival, proliferation and activation. Thus, expansion strategies have been focused either to substitute these factors using autologous feeder cells or to use genetically modified allogeneic feeder cells. Recent developments in the clinical use of genetically modified NK cell lines with chimeric antigen receptors, the development of expansion protocols for the clinical use of NK cell from human embryonic stem cells and induced pluripotent stem cells are challenging improvements for NK cell-based immunotherapy. Transfer of several of these protocols to clinical-grade production of NK cells necessitates adaptation of good manufacturing practice conditions, and the development of freezing conditions to establish NK cell stocks will require some effort and, however, should enhance the therapeutic options of NK cells in clinical medicine.

Keywords: Hematopoietic stem cell transplantation; Immunotherapy; Killer cell immunoglobulin-like receptor; Natural killer cells.


Fig. 1
Fig. 1
Schematic view of NK cell KIR receptor inhibition by C1, C2 and Bw4 ligands expressed by recipient tumor cells. a The patient expresses C1, C2 and Bw4 KIR ligands and KIR2DL1-, KIR2DL2/3- and KIR3DL1-positive donor NK cells are inhibited (KIR–HLA match, no KIR–ligand missing). b The patient expresses C1, and Bw4 KIR ligands (C2 is missing), single-KIR2DL1+ donor NK cells are not inhibited and can take part in the graft-versus-tumor effect (KIR–HLA mismatch, KIR–ligand missing)

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