Figure 3.
huXBR1-402-PNU suppressed leukemic growth and increased overall survival in models of aggressive human and murine ROR1+ leukemia. (A) 697 ROR1+ ALL disseminated leukemia model. Kaplan-Meier survival curve showing death of mice in each treatment group (trastuzumab-G5-PNU [Tras-G5-PNU] and XBR1-402-G5-PNU). Mice were treated intravenously with 1 mg/kg of drug on days 7 and 14 after implantation. Survival data were analyzed with log-rank test. n = 6 mice per group. (B) Schematic showing the experimental design for establishing human ROR1-expressing murine TCL1 model of CLL and intraperitoneal dosing scheme for fully humanized huXBR1-402. Briefly, C57BL/6 mice were engrafted with 5 × 106 huROR1-TCL1 spleen-derived leukemic cells via tail vein injection. All mice were treated with 1 mg/kg of either huXBR1-402-G5-PNU, Tras-G5-PNU, or equal volumes of vehicle 3 times per week for 1 week after enrollment criteria were met (peripheral leukemia proportion was >5% of total white blood cells). (C) Weekly peripheral leukemia cell counts of a single mouse cohort as determined by flow cytometry. Mixed effects model was used to analyze differences with P value given at week 6. n = 4 mice per group. (D) Kaplan-Meier survival curve showing death of mice in each treatment group (vehicle, trastuzumab-PNU, unconjugated huXBR1-402, and huXBR1-402 PNU). Survival data were analyzed by using the log-rank test. n = 9 mice per group. Error bars indicate ± SE.

huXBR1-402-PNU suppressed leukemic growth and increased overall survival in models of aggressive human and murine ROR1+ leukemia. (A) 697 ROR1+ ALL disseminated leukemia model. Kaplan-Meier survival curve showing death of mice in each treatment group (trastuzumab-G5-PNU [Tras-G5-PNU] and XBR1-402-G5-PNU). Mice were treated intravenously with 1 mg/kg of drug on days 7 and 14 after implantation. Survival data were analyzed with log-rank test. n = 6 mice per group. (B) Schematic showing the experimental design for establishing human ROR1-expressing murine TCL1 model of CLL and intraperitoneal dosing scheme for fully humanized huXBR1-402. Briefly, C57BL/6 mice were engrafted with 5 × 106 huROR1-TCL1 spleen-derived leukemic cells via tail vein injection. All mice were treated with 1 mg/kg of either huXBR1-402-G5-PNU, Tras-G5-PNU, or equal volumes of vehicle 3 times per week for 1 week after enrollment criteria were met (peripheral leukemia proportion was >5% of total white blood cells). (C) Weekly peripheral leukemia cell counts of a single mouse cohort as determined by flow cytometry. Mixed effects model was used to analyze differences with P value given at week 6. n = 4 mice per group. (D) Kaplan-Meier survival curve showing death of mice in each treatment group (vehicle, trastuzumab-PNU, unconjugated huXBR1-402, and huXBR1-402 PNU). Survival data were analyzed by using the log-rank test. n = 9 mice per group. Error bars indicate ± SE.

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