Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model

// Takashi Murakami 1,2,3 , Jonathan DeLong 2 , Fritz C. Eilber 5 , Ming Zhao 1 , Yong Zhang 1 , Nan Zhang 1 , Arun Singh 4 , Tara Russell 5 , Samantha Deng 1 , Jose Reynoso 1 , Cuong Quan 1 , Yukihiko Hiroshima 3 , Ryusei Matsuyama 3 , Takashi Chishima 3 , Kuniya Tanaka 3 , Michael Bouvet 2 , Sant Chawla 6 , Itaru Endo 3 and 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 Division of Surgical Oncology, University of California, Los Angeles, California, USA 6 Sarcoma Oncology Center, Santa Monica, California, USA Correspondence to: Robert M. Hoffman, email: // Fritz C. Eilber, email: // Keywords : nude mice, patient-derived orthotopic xenograft, soft tissue sarcoma, Salmonella typhimurium A1-R, tumor-targeting Received : January 12, 2015 Accepted : January 27, 2016 Published : February 07, 2016 Abstract A patient with high grade undifferentiated pleomorphic soft-tissue sarcoma from a striated muscle was grown orthotopically in the right biceps femoris muscle of mice to establish a patient-derived orthotopic xenograft (PDOX) model. Twenty PDOX mice were divided into 4 groups: G1, control without treatment; G2, Salmonella typhimurium ( S. typhimurium )A1-R administered by intratumoral (i.t.) injection once a week for 4 weeks; G3, doxorubicin (DOX) administered by intraperitoneal (i.p.) injection once a week for 4 weeks; G4, S. typhimurium A1-R (i.t.) administered once a week for 2 weeks followed by i.p. doxorubicin once a week for 2 weeks. On day 25 from the initiation of treatment, tumor volume in G2, G3, and G4 was significantly lower than G1. Mice found without gross tumor included one mouse (20%) in G2; one mouse (20%) in G3; and 3 mice (60%) in G4. Body weight loss did not significantly differ between the 3 treated groups or from the untreated control. Histological examination revealed eradication of tumor only in G4 where mice were treated with S. typhimurium A1-R followed by DOX. Our present study indicates future clinical potential of combining S. typhimurium A1-R with chemotherapy such as DOX for soft tissue sarcoma patients.