Figure 1.

The HCA-EFZP-IL-12 vector as a therapy for osteosarcoma

(A). Schematic illustration showing the backbone of the HC-AdV HCA-EFZP-IL-12. The adenovirus encodes mouse IL-12 (mIL-12) with a mifepristone (RU-486)-inducible system for controlled expression of IL-12. (B) Scheme of the experimental schedule. K7M2 murine osteosarcoma cells (5 × 10⁵ per tibia) were injected into the tibial tuberosity of BALB/c mice (day −10). Animals were treated twice intratumorally with either a saline solution (control group) or 2 × 10⁸ IU of HCA-EFZP-IL-12 (days −5 and −7). 3 days later, both groups were administered mifepristone intraperitoneally for 2 weeks with increasing doses (1 mg/kg on days 0–4, 4 mg/kg on days 7–9, and 8 mg/kg on days 10 and 11). Animals were sacrificed when they presented symptoms of disease, or the tumor volume reached 430 mm³. (C) Serum concentrations of IL-12 determined 10 h after mifepristone induction on the indicated days. (D) Determination of IL-12 specificity expression after mifepristone induction. K7M2 cells were engrafted into the tibial tuberosity following the same schedule as (B). Animals were randomized to four groups and serum concentration of IL-12 determined 10 h after mifepristone induction on the indicated days. The groups were as follows: (1) control without mifepristone (PBS−), (2) control plus mifepristone (PBS+), (3) HCA-EFZP-IL-12 without mifepristone (HCA-IL-12−), and (4) HCA-EFZP-IL-12 plus mifepristone (HCA-IL-12+).