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

Tasuku Kiyuna, Takashi Murakami, Yasunori Tome, Kei Kawaguchi, Kentaro Igarashi, Yong Zhang, Ming Zhao, Yunfeng Li, Michael Bouvet, Fuminori Kanaya, Arun Singh, Sarah Dry, Fritz C. Eilber, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)33046-33054
Number of pages9
JournalOncotarget
Volume7
Issue number22
DOIs
Publication statusPublished - 2016 May 31

Keywords

  • Doxorubicin
  • GFP
  • Nude mice
  • PDOX
  • Salmonella typhimurium A1-R
  • Sarcoma
  • Soft-tissue
  • Tumor-targeting

ASJC Scopus subject areas

  • Oncology

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