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. 2021 Jun 4;13(11):2796. doi: 10.3390/cancers13112796

Figure 2.

Figure 2

Approaches to clinical applications of adoptive NK cell therapy. Sources of NK cells may originate from an autologous donor or allogeneic donor, which will influence how they are collected. Peripheral blood mononuclear cells from autologous donors are collected using leukapheresis and may be subject to KIR genotyping, whereas peripheral blood mononuclear cells from allogeneic donors may be subject to HLA and KIR genotyping. Other allogeneic sources of NK cells include NK cells from cord blood, a cell line such as NK-92 cells, or NK cells derived from induced pluripotent stem cells (iPSC). These sources of NK cells offer the benefit of being an “off-the-shelf” adoptive cell therapy. NK cells require expansion and activation through cytokines, such as IL-2, IL-12, IL-15, IL-18, or IL-21. Membrane bound (mb) IL-15 or IL-21 with 41BB ligand have been genetically engineered into feeder cell lines, such as K562 cells, to generate robust NK expansions. NK cells can be genetically modified to express CARs that enable them to target a specific antigen. Recent developments in CAR NK technology have found that co-expression of IL-15 enhances CAR NK persistence, therefore obviating the need for systematic administration of IL-15. Abbreviations: HLA—human leukocyte antigen, KIR—killer immunoglobulin-like receptor, CAR—chimeric antigen receptor.