FIG. 6.
Cytotoxicity and target-specific activation of CAR-transduced in vitro-differentiated NK cells. (a) Cytotoxicity of in vitro-differentiated NK cells against Raji cells (p<0.0001), nontransduced (white circles), CD19R-transduced (black circles), or CD19RCD28-transduced NK cells (white triangles). Values represent arithmetic means of results from 18 experiments, error bars represent mean+SEM, and asterisks indicate statistical significance. (b) Cytotoxicity against Raji (p=0.0035), K562 (p=0.0035), and CD19-K562 cells of in vitro-differentiated NK cells, nontransduced (NT, white columns), luciferase-transduced (LUC, light gray), CD19R-transduced (dark gray), or CD19RCD28-transduced (black columns) at a 10:1 E:T ratio. Values represent arithmetic means of results from four experiments and error bars represent mean+SEM. (c) Cytotoxicity of primary T-cells (p<0.0001) and in vitro-differentiated myeloid cells (p<0.0001) and NK cells (p=0.02), nontransduced (white columns) or transduced with CD19R (gray columns) or CD19RCD28 (black columns) against Raji cells at a 20:1 E:T ratio, adjusted by percentage of mature cells (NK cells) and CD19-specific CAR expression (T-cells and myeloid cells). Values represent arithmetic means of results from 18 experiments, error bars represent mean+SEM, and asterisks indicate statistical significance. (d) IFN-γ ELISPOT assay of in vitro-differentiated NK cells, nontransduced (NT) and transduced with EGFP, firefly luciferase (LUC), CD19R, or CD19RCD28, against Raji cells (p=0.006). Values represent arithmetic means of results from four experiments and error bars represent mean+SEM.