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

// Takashi Murakami 1, 2, 3 , Kentaro Igarashi 1 , Kei Kawaguchi 1 , Tasuku Kiyuna 1 , Yong Zhang 1 , Ming Zhao 1 , Yukihiko Hiroshima 3 , Scott D. Nelson 5 , Sarah M. Dry 5 , Yunfeng Li 5 , Jane Yanagawa 6 , Tara Russell 6 , Noah Federman 7 , Arun Singh 4 , Irmina Elliott 6 , Ryusei Matsuyama 3 , Takashi Chishima 3 , Kuniya Tanaka 3 , Itaru Endo 3 , Fritz C. Eilber 6 , Robert M. Hoffman 1, 2 1 AntiCancer, Inc., San Diego, California, USA 2 Department of Surgery, University of California, San Diego, California, USA 3 Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan 4 Division of Hematology-Oncology, University of California, Los Angeles, California, USA 5 Department of Pathology, University of California Los Angeles, California, USA 6 Division of Surgical Oncology, University of California, Los Angeles, California, USA 7 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 Correspondence to: Robert M. Hoffman, email: all@anticancer.com Fritz C. Eilber, email: fceilber@mednet.ucla.edu Keywords: osteosarcoma, nude mouse, patient-derived xenograft, Salmonella typhimurium A1-R, tumor-targeting Received: October 20, 2016      Accepted: November 16, 2016      Published: December 20, 2016 ABSTRACT 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.