p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death.

作者信息

Demiya Koji, Tazawa Hiroshi, Kondo Hiroya, Kure Miho, Mochizuki Yusuke, Komatsubara Tadashi, Yoshida Aki, Uotani Koji, Hasei Joe, Fujiwara Tomohiro, Kunisada Toshiyuki, Urata Yasuo, Kagawa Shunsuke, Ozaki Toshifumi, Fujiwara Toshiyoshi

机构信息

Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

出版信息

Mol Ther Oncol. 2024 Jun 29;32(3):200845. doi: 10.1016/j.omton.2024.200845. eCollection 2024 Sep 19.

Abstract

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/399c/11300929/732db4a5dd40/fx1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索