Figure 5.
Immunotherapeutic approaches are able to overcome BAX-dependent and -independent VEN resistance. (A-B) Viability assays of Nalm6, DOHH-2, 697, and OSU cells (Ctrl, BAX−/− #7, BAX−/− #12) incubated with activated PBMCs (tumor:effector ratio of 10:1) and blinatumomab (50 ng/mL, 24/48 hours). Percentage of annexin-V+, CD4, and CD8− cells was determined by flow cytometry, normalized to PBMC cocultured, untreated cells. N = 4; P < .001; paired t test. (C) Viability of sensitive and VEN-resistant Nalm6 cells and OSU-CLL wild-type and BAX−/− clones after treatment with anti-CD19 CAR T cells determined by an XTT assay. Representative experiment of N = 3 experiments shown. Susceptibility toward CAR T-cell killing was not statistically different between sensitive and resistant cells. ∗∗P < .01; ∗∗∗P < .001. Ctrl, control; w/o, without.

Immunotherapeutic approaches are able to overcome BAX-dependent and -independent VEN resistance. (A-B) Viability assays of Nalm6, DOHH-2, 697, and OSU cells (Ctrl, BAX−/− #7, BAX−/− #12) incubated with activated PBMCs (tumor:effector ratio of 10:1) and blinatumomab (50 ng/mL, 24/48 hours). Percentage of annexin-V+, CD4, and CD8− cells was determined by flow cytometry, normalized to PBMC cocultured, untreated cells. N = 4; P < .001; paired t test. (C) Viability of sensitive and VEN-resistant Nalm6 cells and OSU-CLL wild-type and BAX−/− clones after treatment with anti-CD19 CAR T cells determined by an XTT assay. Representative experiment of N = 3 experiments shown. Susceptibility toward CAR T-cell killing was not statistically different between sensitive and resistant cells. ∗∗P < .01; ∗∗∗P < .001. Ctrl, control; w/o, without.

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