High efficacy of tumor-targeting Salmonella typhimurium A1-R on a doxorubicin- and dactolisib-resistant follicular dendritic-cell sarcoma in a patient-derived orthotopic xenograft PDOX nude mouse model
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Tasuku Kiyuna1,2,3, Takashi Murakami1,2, Yasunori Tome3, Kei Kawaguchi1,2, Kentaro Igarashi1,2, Yong Zhang1, Ming Zhao1, Yunfeng Li5, Michael Bouvet2, Fuminori Kanaya3, Arun Singh4, Sarah Dry5, Fritz C. Eilber6, Robert M. Hoffman1,2,7
1AntiCancer Inc., San Diego, CA, USA
2Department of Surgery, University of California, San Diego, CA, USA
3Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
4Division of Hematology-Oncology, University of California, Los Angeles, CA, USA
5Department of Pathology, University of California, Los Angeles, CA, USA
6Division of Surgical Oncology, University of California, Los Angeles, CA, USA
7PDOX LLC, San Diego, CA, USA
Robert M. Hoffman, email: [email protected]
Fritz C. Eilber, email: [email protected]
Keywords: Salmonella typhimurium A1-R, tumor-targeting, GFP, sarcoma, soft-tissue
Received: February 23, 2016 Accepted: March 31, 2016 Published: April 20, 2016
Follicular dendritic-cell sarcoma (FDCS) is a rare and recalcitrant disease. In the present study, a patient-derived orthotopic xenograft (PDOX) mouse model of FDCS was established in the biceps muscle of nude mice. The FDCS PDOX was resistant to both doxorubicin (DOX) and NVP-BEZ235, dactolisib (BEZ) an experimental agent which is a dual pan-phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor. However, in contrast to DOX and BEZ, the FDCS PDOX was sensitive to the tumor-targeting bacterial strain, Salmonella typhimurium A1-R (S. typhimurium A1-R). The combination of S. typhimurium A1-R and either DOX or BEZ did not increase the antitumor efficacy of S. typhimurium A1-R, indicating that DOX and BEZ were not active in this PDOX model. The efficacy of S. typhimurium A1-R in this recalcitrant FDCS gives strong impetus to move bacterial therapy to clinical trials for this disease. The findings of the present study are of particular importance since it demonstrates that S. typhimurium A1-R is effective in a PDOX model of FDCS established from a patient who failed DOX therapy.
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