Birinapant synergizes with anti-CD3 to inhibit leukemia expansion. (A) NSG mice infused with 106 leukemic cells from the PDXs derived from the indicated T-ALL cases were monitored for leukemia expansion over time. Once leukemic, mice (n = 4 per group) were treated 6 times with either 4 μg of control IgG2a/carrier solvent (blue), or OKT3/carrier solvent (red), or IgG2a/birinapant (20 mg/kg, green), or OKT3 + birinapant (purple), every 3 to 4 days. In the left part of the panel, leukemic load is measured at the end of treatment. For UPNT420- and 757-derived T-ALL xenografts, mice treated with OKT3/carrier solvent were found to be in remission for 70 (UPNT420) and 110 (UPNT757) days, respectively, after beginning of the treatment but relapsed thereafter. The right part of the panel shows leukemia load at day 102 days (UPNT420) and day 171 (UPNT757), respectively, after beginning of treatment. Note that at these time points, OKT3 + birinapant–treated mice are leukemia free. (B) Kaplan-Meier survival curves of NSG mice transplanted with T-ALL M149, UPNT663, UPNT-760, UPNT776, or UPNT-420 of the cohorts described in panel A. (C) The same experimental protocol was used for PDXs derived from T-ALL UPNT663, UPNT760, and UPNT420 using the clinically relevant anti-CD3 teplizumab. (D) Kaplan-Meier survival curves of NSG mice transplanted with T-ALL UPNT-760 and treated as in panel C. ∗P < 0.05; ∗∗P < 0.01; ∗∗∗P < 0.001.
