Figure 1.
IL-7 and IL-12 encoded in an oncolytic vaccinia virus improves the immune status of tumors and induces complete tumor regression (CR)
(A) Schematic overview of Cont-VV, hIL-7-VV, mIL-12-VV, and hIL-7/mIL-12-VV. VGF and O1L are functionally deleted by insertion of transgenes as indicated. B5R is modified such that the short consensus repeat domains of B5R are deleted. (B–D) CT26.WT tumors on the right flank of BALB/c mice were treated with vehicle solution, 2 × 107 PFUs of Cont-VV, or 2 × 107 PFUs of hIL-7/mIL-12-VV (n = 6 per group). The day after treatment the tumors were collected, and the concentrations of hIL-7 (B), murine IL-12 (C), and murine IFN-γ (D) were measured. (E and F) Nineteen days after treatment, tumor-infiltrating CD4+ T cells (E) and CD8+ T cells (F) were analyzed by flow cytometry (n = 11–12). Data in (B)–(F) are mean ± SEM. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001 by Mann-Whitney U test. (G) Vehicle solution, hIL-7/mIL-12-VV at a dose of 2 × 105, 2 × 106, and 2 × 107 PFUs were intratumorally injected into CT26.WT tumors every other day, a total of three times. Growth of individual tumors in mice treated with vehicle or hIL-7/mIL-12-VV is shown. Mean tumor volume for each group is shown by the red line. Ratios of mice that achieved CR by day 28 are shown (n = 6). (H) 2 × 107 PFUs of Cont-VV was intratumorally injected as in (G). Growth of individual tumors in mice treated with Cont-VV is shown (n = 6).