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.
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.
AntiCancer Inc., San Diego, CA, USA.|Department of Surgery, University of California, San Diego, CA, USA.|Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Tasuku
T
Kiyuna
AntiCancer Inc., San Diego, CA, USA.|Department of Surgery, University of California, San Diego, CA, USA.
Takashi
T
Murakami
Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Yasunori
Y
Tome
AntiCancer Inc., San Diego, CA, USA.|Department of Surgery, University of California, San Diego, CA, USA.
Kei
K
Kawaguchi
AntiCancer Inc., San Diego, CA, USA.|Department of Surgery, University of California, San Diego, CA, USA.
Kentaro
K
Igarashi
AntiCancer Inc., San Diego, CA, USA.
Yong
Y
Zhang
AntiCancer Inc., San Diego, CA, USA.
Ming
M
Zhao
Department of Pathology, University of California, Los Angeles, CA, USA.
Yunfeng
Y
Li
Department of Surgery, University of California, San Diego, CA, USA.
Michael
M
Bouvet
Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Fuminori
F
Kanaya
Division of Hematology-Oncology, University of California, Los Angeles, CA, USA.
Arun
A
Singh
Department of Pathology, University of California, Los Angeles, CA, USA.
Sarah
S
Dry
Division of Surgical Oncology, University of California, Los Angeles, CA, USA.
Fritz C
FC
Eilber
AntiCancer Inc., San Diego, CA, USA.|Department of Surgery, University of California, San Diego, CA, USA.|PDOX LLC, San Diego, CA, USA.
Robert M
RM
Hoffman
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D054740:Dendritic Cell Sarcoma, Follicular / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D011804:Quinolines / Q000494:pharmacology; D012480:Salmonella Infections / Q000473:pathology; D012486:Salmonella typhimurium / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D007093:Imidazoles; D011804:Quinolines; D004317:Doxorubicin; C531198:dactolisib
GFP; Salmonella typhimurium A1-R; sarcoma; soft-tissue; tumor-targeting