. 2020 Jan 17;10:3013. doi: 10.3389/fimmu.2019.03013

Table 1.

Human NK cell-based immunotherapeutic approaches in tumors.

1. Adoptive NK cell therapies
- Infusion of IL-2- or IL-15-activated NK cells or lymphokine-activated lymphocytes (LAK and CIK) (8–11);
- Infusion of allogeneic “off-the-shelf” CAR-NK cells directed to tumor antigens (12).

2. NK cells in haplo-HSCT to cure high-risk leukemia
- Transplant of “pure” donor CD34⁺ cells. NKG2A⁺ NK cells are detectable after 2 weeks, while KIR⁺, cytolytic NK cells only after 6–8 weeks. Central role of NK cells in GvL, especially of “alloreactive” NK cells (13, 14);
- Transplant of αβT- and B cell-depleted mononuclear cells. Donor NK cells and γδT cells, being present in the graft, are immediately available for the control of infections and leukemia relapses. Better clinical outcome, particularly in AML (15–19).

3.mAbs blocking inhibitory checkpoints in NK cells
- The disruption of PD1/PD-L1 interactions unleashes both PD1⁺ T and NK cells. Major effect of NK cells in case of HLA-Cl-I⁻ tumors (20–24);
- Blocking of NKG2A expressed by both NK and tumor-infiltrating T cells results in killing of HLA-E⁺ tumors (i.e., most tumors) (25, 26);
- Combined blocking of NKG2A and PD1 in case of PD-L1⁺ tumors (25, 26);
- Combined use of NKG2A-blocking mAb and mAb specific for tumor antigens (e.g., EGFR): “unlocked” NK cells mediate ADCC (25, 26).