Radio-immune fusion therapy for cancer; ER stress loading with radiation and celecoxib

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We found that the anti-inflammatory drug celecoxib significantly enhanced the radiosensitivity of mouse glioblastoma cells GL261 by loading ER stress. Based on this, we established GL261 cells constitutively expressing monomeric Kusabira-Orange (GL261-mKO) that were used to generate a mouse thigh subcutaneous tumor model in syngenic albino C57BL/6 mice, in which tumor size can be monitored by an in vivo imaging system. In experiments with local X-ray irradiation (IR) to tumors in this system, the cure rate was significantly higher with the concomitant oral administration of 5mg/kg of celecoxib as compared to IR alone. Furthermore, the same tumor cells that were re-challenged to the brain in the cured mice were all rejected, while they grew rapidly in mice that showed tumor regrowth after IR. ELISPOT assay demonstrated that IFN-gamma level was significantly elevated in mice that rejected re-challenged tumor cells, indicating that anti-tumor cellular immunity was established.