Table 1.
Protocol features | Starting material/culture system | NK cell expansion rate | NK cell purity | NK cell phenotype | NK cell function | Setting | Reference |
---|---|---|---|---|---|---|---|
IL-2 + IL-15 | PBMC, CD3 depleted and CD56 enriched or PBMC, CD3/CD19 depleted in flasks | >1 (5 days) | 75–100% NK ≤0.1% T cells |
Upregulated: CD69, NKp30, and NKp44 | Cytolysis of leukemia cell lines and primary acute leukemic blasts | In vitro | (51) |
IL-2 | PBMC, CD3 depleted, and CD56 enriched in bags and flasks | 4–5 (12–14 days) | ~92–95% NK <0.1% T cells |
increased CD56+CD16− frequency; increased p-STAT3 and p-AKT; increased lytic activity, upregulation of CD69, NKG2D, and natural cytotoxicity receptors (NCRs); increasing amount of NK cells without killer cell immunoglobulin-likereceptors | Improved cytotoxic activity against leukemia and tumors | Clinical | (26, 52, 53) |
IL-15 | Isolated CD3−CD56+ cells | N/A (2–5 weeks) | 94–99% NK | Enhanced killing via NCRs, DNAM-1 and NKG2D | Enhanced cytolysis of lymphoma and rhabdomyosarcoma cell lines via NCRs | In vitro | (54) |
IL-2 + IL-21 | PBMC, sorted for CD3−CD56+ | None with IL-21 only; strongly with IL-2 + IL-21 | N/A | Upregulated: CD69, CD25; activation of STAT3 | Enhanced cytotoxicity against K562 | In vitro | (55) |
IL-12 + IL-15 + IL-18 | PBMC, sorted for CD3−CD56+ cells PBMC, CD3 depleted and CD56 enriched |
N/A (12–16 h) | ≥90% NK |
Upregulated: CD94, NKG2A, NKp30, NKp44, NKG2D, NKp46, CD69, and CD25 Downregulated: NKp80 |
Memory: increased IFN-γ production upon stimulation that is preserved during cell division Responsive to picomolar concentrations of IL-2 |
In vitro Clinical |
(56–59) |