Figure 1.

IBL-202 and venetoclax are synergistic against CLL cells. (A) Dose responses for IBL-202 and venetoclax, alone and in combination, at a ratio of 1:100 against primary CLL cells cocultured with CD40L-expressing fibroblasts (n = 10) or HS-5 stromal cells (n = 6) as indicated. The viability of CLL cells was assessed by DilC₁(5)/PI staining and flow cytometry after 48 hours of treatment. Flow cytometric data from 1 representative patient sample illustrates the viability of CLL cells cocultured with CD40L fibroblasts after treatment with IBL-202 and venetoclax at 0.5 µM and 5 nM, respectively, alone or in combination. Results are expressed relative to vehicle-treated control cultures. (B) CI plot (left) and isobologram (right) for IBL-202 and venetoclax in combination against CLL patient samples (n = 10) cocultured with CD40L-expressing fibroblasts illustrates synergy between the 2 drugs. Data are presented as the CI over a range of fractional effects, where a fractional effect value of 0.5, for example, is indicative of 50% cell kill. (C) The proportion of viable CLL and T cells in mixed PBMC fractions from 4 CLL patients before and after drug treatment were determined by flow cytometry using antibodies to CD19 and CD5. PBMC fractions from CLL patients were treated with IBL-202 (1 μM) or venetoclax (10 nM) or the combination for 24 hours in medium. Representative plots from 1 patient are shown.