Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug.

Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model.

Oncotarget. 2017 Jan 31 [Epub]

Takashi Murakami, Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Yong Zhang, Ming Zhao, Yukihiko Hiroshima, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara Russell, Noah Federman, Arun Singh, Irmina Elliott, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, Itaru Endo, Fritz C Eilber, Robert M Hoffman

AntiCancer, Inc., San Diego, California, USA., Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan., Department of Pathology, University of California Los Angeles, California, USA., Division of Surgical Oncology, University of California, Los Angeles, California, USA., Department of Pediatrics and Department of Orthopaedics, David Geffen School of Medicine, Mattel Children's Hospital, UCLA's Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA., Division of Hematology-Oncology, University of California, Los Angeles, California, USA.