Combining Tumor-Selective Bacterial Therapy with Salmonella typhimurium A1-R and Cancer Metabolism Targeting with Oral Recombinant Methioninase Regressed an Ewing's Sarcoma in a Patient-Derived Orthotopic Xenograft Model

Kentaro Miyake, Tasuku Kiyuna, Shukuan Li, Qinghong Han, Yuying Tan, Ming Zhao, Hiromichi Oshiro, Kei Kawaguchi, Takashi Higuchi, Zhiying Zhang, Sahar Razmjooei, Maryam Barangi, Sintawat Wangsiricharoen, Takashi Murakami, Arun S. Singh, Yunfeng Li, Scott D. Nelson, Fritz C. Eilber, Michael Bouvet, Yukihiko HiroshimaTakashi Chishima, Ryusei Matsuyama, Shree Ram Singh, Itaru Endo, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Background: Ewing's sarcoma (ES) is a recalcitrant disease in need of transformative therapeutics. Objectives: The aim of this study was to investigate the efficacy of tumor-selective Salmonella typhimurium A1-R combined with tumor metabolism targeting with oral administration of recombinant methioninase (o-rMETase), on an ES patient-derived orthotopic xenograft (PDOX) model. Methods: The ES PDOX models were previously established in the right chest wall. The ES PDOX models were randomized into 5 groups when the tumor volume reached 80 mm 3 : G1: untreated control; G2: doxorubicin; G3: S. typhimurium A1-R; G4: o-rMETase; G5: S. typhimurium A1-R combined with o-rMETase. All mice were sacrificed on day 15. Body weight and tumor volume were assessed twice a week. Results: S. typhimurium A1-R and o-rMETase respectively suppressed tumor growth as monotherapies (p = 0.050 and p = 0.032). S. typhimurium A1-R combined with o-rMETase regressed tumor growth significantly compared to untreated group on day 15 (p < 0.032). S. typhimurium A1-R combined with o-rMETase group was significantly more effective than S. typhimurium A1-R or o-rMETase monotherapy (p = 0.032, p = 0.032). Conclusions: The present results suggest that the combination of S. typhimurium A1-R and o-rMETase has promise to be a transformative therapy for ES.

Original languageEnglish
Pages (from-to)278-283
Number of pages6
JournalChemotherapy
Volume63
Issue number5
DOIs
Publication statusPublished - 2019 Feb 1
Externally publishedYes

Keywords

  • Bacterial therapy
  • Ewing's sarcoma
  • Methioninase
  • Patient-derived orthotopic xenograft
  • Patient-derived orthotopic xenograft nude mice
  • Salmonella typhimurium A1-R
  • Transformative therapy

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)
  • Infectious Diseases

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