Figure 7.
MSC-TERT-tetoneE1B55K-GRP78 significantly enhances in vivo antitumor efficacy of oncolytic adenovirus
(A) Schematic overview of the animal study procedure. (B) Tumor volume measurement in A549 xenograft models. Tumor cells were implanted subcutaneously in the flank region of BALB/c athymic nude mice, and 1 × 106 MSC-TERT-tetoneE1B55K-GRP78 or MSC-TERT-tetoneE1B55K-GRP78 loaded with oncolytic adenovirus was injected intravenously twice with an interval of 3 days. Tumor volume was monitored and recorded every 2 days until the end of the study. Arrows indicate when the MSC or oncolytic adenovirus/MSC complex was administered. Error bars represent mean ± SD from 10 mice per group: ∗∗p < 0.01, ∗∗∗∗p < 0.0001. (C and D) All mice in each experimental group (C) and tumor tissues of mice obtained by necropsy (D) at the end of the experiment. Every mouse was individually tracked. (E) The expression of adenovirus type 5 structural protein in tumor tissues was analyzed by immunohistochemistry at 7 days after the second intravenous injection. Representative images show the average of all slides for each group. Rows 2 and 4 are enlarged images of the black squares in rows 1 and 3. Scale bars, 100 μm. (F) Tumor volume measurements in A549 xenograft models using lower number of modified MSCs. Tumor cells were implanted subcutaneously in the flank region of BALB/c athymic nude mice, and 2 × 105 MSC-TERT-tetoneE1B55K or MSC-TERT-tetoneE1B55K-GRP78 loaded with oncolytic adenovirus (Ad-3484-shHSP27-shTGF-β1) was injected intravenously twice with an interval of 3 days. Tumor volume was monitored for 30 days and recorded every 2 days. Error bars represent mean ± SD from 10 mice per group. (G) All tumor tissues of mice in each experimental group (no treatment, Ad-3484-shHSP27-shTGF-β1/MSC-TERT-tetoneE1B55K, and Ad-3484-shHSP27-shTGF-β1/MSC-TERT-tetoneE1B55K-GRP78) were obtained by necropsy at the end of the experiment. Every mouse was individually tracked.