Figure 7.

mAb-mediated disruption of DNAM-1/ligands interaction inhibits the NK-mediated lysis of PVR or Nectin-2 cell transfectants and of tumor cell targets. (A) NK92 or YT NK cell lines were analyzed for cytolytic activity against the CHO-K cells either untransfected or transfected with PVRα or Nectin-2δ constructs. Cytolytic assays were performed either in the absence of mAb (white bars) or in the presence of F252, GN18, L14, and L95 mAbs to the indicated molecules (black bars). The effector/target ratio used was10:1 for NK92 and 40:1 for YT. Similar results were obtained with Nectin-2α transfectants (data not shown). (B) NK92 NK cell line pretreated with anti-NKG2D mAb (for 15 min at room temperature) was analyzed for cytolytic activity against the indicated tumor target cells in the presence of either a control mAb (white bars) or mAbs (as in panel A) to the indicated molecules (black bars). The effector/target ratio used was 10:1. (C) A polyclonal NK cell population pretreated with anti-NKG2D mAb was analyzed for cytolytic activity against the indicated tumor target cells in the presence of either a control mAb (white bars) or mAbs to NCR (F252 and KL247), DNAM-1 (KRA236), or DNAM-1-Ligands (L95 and L14). These mAbs were used alone or in combination as indicated. The effector/target ratio used was 4:1. The results are representative of four independent experiments; the standard deviation of the mean of the triplicates was <4%.