Abstract 1794: Preclinical evaluation of radiotherapy in combination with radio-sensitizing telomerase-specific oncolytic virus for human bone and soft tissue sarcomas
Authors: Omori Toshinori , Yamakawa Yasuaki , Hasei Joe , Tazawa Hiroshi , Osaki Shuhei , Sasaki Tusyoshi , Sugiu Kazuhisa , Fujiwara Tomohiro , Kunisada Toshiyuki , Urata Yasuo , Ozaki Toshifumi , Fujiwara Toshiyoshi 
Published: August 2015

Abstract
Background: Despite major advances in the treatment of bone and soft tissue sarcomas, including surgery, chemotherapy, and radiation, some sarcoma patients show poor prognosis due to resistance to conventional therapy. Therefore, the development of a novel therapeutic strategy for sarcoma patients is needed. We recently revealed that a telomerase-specific, replication-competent oncolytic adenovirus OBP-301 efficiently killed human sarcoma cells. Moreover, combination therapy with OBP-301 and radiation has been confirmed to show synergistic antitumor effect in epithelial malignant tumor cells; however, its effect in human sarcoma cells remains elusive. In this study, we investigated the antitumor effect of OBP-301 in combination with radiation against human sarcoma cells.
Methods: We used five human sarcoma cell lines, SK-ES-1 (Ewing sarcoma), RD-ES (Ewing sarcoma) SYO-1 (synovial sarcoma), U2OS (osteosarcoma) and HOS (osteosarcoma). Cells were irradiated 24 h after infection with OBP-301, and cell viability was assessed by XTT assay 4 days after irradiation. Combined effect of radiation with OBP-301 was analyzed with the CalcuSyn software (BioSoft). These cells were analyzed for apoptosis using western blot analysis. To analyze the effect of OBP-301 in DNA repair process, immunofluorescence staining was performed after treatment of irradiation with or without OBP-301 infection on SK-ES-1 cell. We further investigated the in vivo combined effect of OBP-301 and radiation. The SK-ES-1 tumor-bearing mice were irradiated at a dosage of 1 Gy/tumor once per week for three cycles, and OBP-301 (1 × 108 plaque-forming units per tumor), or PBS was injected into the tumor 3 times per week for three cycles.
Results: Combination treatment with OBP-301 and radiation showed synergistic or additive antitumor effect in all human sarcoma cells. Western blot analysis showed that combination treatment increased the expression of cleaved-PARP, and prolonged the level of γH2AX protein than radiation treatment. Combination therapy of OBP-301 with radiation showed antitumor effect more significantly than monotherapy in SK-ES-1 xenograft tumor model.
Conclusions: These results suggest that combination therapy of OBP-301 with radiation is a promising antitumor strategy for bone and soft tissue sarcomas.
Citation Format: Toshinori Omori, Yasuaki Yamakawa, Joe Hasei, Hiroshi Tazawa, Shuhei Osaki, Tusyoshi Sasaki, Kazuhisa Sugiu, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara. Preclinical evaluation of radiotherapy in combination with radio-sensitizing telomerase-specific oncolytic virus for human bone and soft tissue sarcomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1794. doi:10.1158/1538-7445.AM2015-1794