Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model
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Takashi Murakami1,2,3, Jonathan DeLong2, Fritz C. Eilber5, Ming Zhao1, Yong Zhang1, Nan Zhang1, Arun Singh4, Tara Russell5, Samantha Deng1, Jose Reynoso1, Cuong Quan1, Yukihiko Hiroshima3, Ryusei Matsuyama3, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet2, Sant Chawla6, Itaru Endo3 and Robert M. Hoffman1,2
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
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
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.
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