Fig. 4
Epitope-distinct murine and humanized anti-DEspR mAbs inhibit PPC dissemination-progression. a Diagram of anti-DEspR ex vivo pre-treatment design evaluating CSC tumorigenicity in Panc1-CSC subcutaneous and PPC xenograft nude-rat models. b Ex vivo pre-treatment with 5g12 (red) 200 μg/mL × 1-h (n = 6) decreased Panc1-CSC tumorigenicity vs saline controls (n = 8) (p < 0.001, repeated t-test. c Ex vivo pre-treatment of Panc1-CSCs with anti-DEspR 5g12 (red, n = 8) and 6g8 (blue/n = 8) (200 μg/ml × 1-h) increased survival vs saline control (black/n = 15) (p = 0.0088, log rank test). d Diagram of in vivo anti-DEspR treatment in PPC nude-rat models. e Survival analysis: PPC-females comparing saline-control (n = 15) vs multi-dose (1 mg/kg ip 2x/wk. × 4 wks) murine anti-DEspR epitope-2 6g8 (n = 8, p = 0.0002), epitope-1 7c5 (n = 7, p = 0.002), and gemcitabine 26 mg/kg (n = 7, ns). f Survival analysis: single-dose-treated PPC-females 3 wks after CSC-ip injection: saline controls (n = 12), hu-6g8 at 3 mg/kg (n = 8, p = 0.001) or 15 mg/kg (n = 7, p = 0.0007), or gemcitabine 100 mg/kg (n = 7, p = 0.0018). g Survival analysis in single-dosed PPC-males: hu-6g8 15 mg/kg/dose (n = 6) vs saline (n = 6, p = 0.02). Kaplan-Meier survival analyses with log rank and Holm-Sidak multiple pairwise comparisons testing (Table S4). h, i Single-dose hu-6g8 pharmacokinetic analysis in PPC-females at t-21 days to match tumor burden and treatment onset to survival studies. Two-compartment analyses at intravenous-dosing: 3 mg/kg (h) and 15 mg/kg (i). T1/2,avg = 46.1 h, maximum retention time (MRTavg) = 65.2 h