Fig. 4.

Therapeutic efficacy of H-Zt/g4-MMAE in PDAC xenograft tumor models: (a) Dose-dependent effect of H-Zt/g4-MMAE: Athymic nude mice (5 mice per group) were subcutaneously inoculated with 5 × 10⁶ FG cells. H-Zt/g4-MMAE at 1, 3, 7, 10, and 15 mg/kg was injected through tail vein in the Q6 × 5 regimen after tumors volumes reached to ~ 150 mm³. Mice injected with CmIgG-MMAE at 10 mg/kg were used as the control. Xenografts initiated by HT-29 cells served for comparison. (b) Effect of H-Zt/g4-MMAE in PDAC xenograft growth and eradication. Individual tumors from different groups described in (A) were collected from euthanized mice. Control mice bearing FG xenografts were sacrificed at day 24 due to rapid growth of tumors. Mice from other groups were killed at day 28 or day 44 dependent on the size of tumors. All tumors were weighted to reach the average tumor weight per group. The number of tumors from individual groups also was counted to determine the eradicating effect of H-Zt/g4-MMAE. NA, no tumors were found in the injected site. (c) Effect of H-Zt/g4-MMAE in three PDAC xenograft models: Xenograft tumors in mice (five animals per group) initiated by four PDAC cell lines were used for study. H-Zt/g4-MMAE was used at 20 mg/kg in the Q12 × 2 schedules. To establish the dose-effect relationship, the estimated reduction of H-Zt/g4-MMAE in vivo according to the t½ was marked as red circles. (d) Effect of H-Zt/g4-MMAE in tumor growth and eradication: Tumors were collected from mice described in (b). Tumor weight, count, and calculation were performed as described in (b). NA, no tumors were observed in the injected site