Cytotoxicity and specificity of LL2-onconase.

(A) Cytotoxicity of conjugated (LL2-Onc) and unconjugated onconase (Onc) to Daudi (circle) or CA-46 (square) cells. Cells were treated with increasing concentrations of LL2-onconase (solid symbols) or onconase (open symbols). (B) LL2 increases the cytotoxicity of onconase. Daudi cells were treated with increasing concentrations of onconase (open circles) or LL2-onconase (solid circles). (C) LL2-onconase cytotoxicity on Daudi lymphoma cells is specific to the CD22 antigen. LL2-onconase cytotoxicy (solid circles) against Daudi cells is inhibited by excess (300 nM) LL2 (open circles); and a nonrelevant IgG2a (UPC-10) antibody-onconase conjugate is not cytotoxic to Daudi cells (solid squares). (D) Cytotoxicity of onconase (open circles) and LL2-onconase (solid circles) toward CD22-negative HUT102 cells. All cells were treated with the test substances for 3 days. Protein synthesis was measured as described in “Materials and methods.” Data are from at least 2 replicate experiments. The SEM of triplicate determinations are shown when they are greater than the symbol.