Fig. 3: Optimization of OT-82 treatment regimen in xenograft tumor models.
a SCID mice carrying SC MV4–11 tumor xenografts were treated PO with OT-82 (60 or 80 mg/kg) when tumors reached 100 mm2 as follows: 3 days treatment/4 days rest (3t/4r), 2t/5r, 3t/7r or 2t/8r regimens. 2t/8r regimen was done only with the dose 80 mg/kg. After three treatment cycles of either regimen, all tumors had disappeared. Treatment was then discontinued, and mice were monitored for relapse for 60 days (n = 10 mice/group). b OT-82 optimized regimen efficacy in systemic AML model. Groups of 9–10 SCID mice were inoculated IV with 107 MV4–11 cells on Day 0 and treated PO with vehicle or OT-82 (20 or 40 mg/kg) on Days 4–20 following the 3t/4r regimen for 3 weeks. Mouse survival was monitored for 90 days after treatment discontinuation. c Effect of OT-82 optimized regimen on tumor growth in SC xenograft model of Burkitt's lymphoma. Mice (SCID) were inoculated with 106 Ramos cells and treated PO with vehicle or OT-82 (60 or 80 mg/kg) 3t/4r for 3 weeks (starting 18 days post inoculation). Mean tumor volume ± SE is shown (n = 16–20 tumors/group). p < 0.05 from Day 22 onwards for both OT-82 treatment groups (Students’ t-test). d OT-82 optimized regimen efficacy in SC xenograft model of multiple myeloma. Mice (SCID) were inoculated SC with 107 RPMI8226 cells and treated PO with vehicle or OT-82 (30 or 60 mg/kg) 3t/4r for 3 weeks starting 29 days post inoculation. Mean tumor volume ± SE is shown in relative units (RU) compared with initial tumor volume (n = 12–16 tumors/group). p < 0.05 from Day 31 onwards for 60 mg/kg OT-82 versus vehicle and from Day 34 onwards for 30 mg/kg OT-82 versus vehicle (Students’ t-test). e OT-82 optimized regimen efficacy in a systemic PDX model of high-risk ALL (ALL-4) [21]. Mice (SCID-NOD) were inoculated IV with 2.5 × 106 PDX cells. PO treatment (3t/4r regimen for 3 weeks) with vehicle or OT-82 (40 mg/kg) was initiated when the median percentage of huCD45 + cells in the peripheral blood of the cohort reached 1%.
