The irony of highly-effective bacterial therapy of a patient-derived orthotopic xenograft (PDOX) model of Ewing's sarcoma, which was blocked by Ewing himself 80 years ago

Takashi Murakami, Tasuku Kiyuna, Kei Kawaguchi, Kentaro Igarashi, Arun S. Singh, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Kentaro Miyake, Scott D. Nelson, Sarah M. Dry, Yunfeng Li, Jonathan C. DeLong, Thinzar M. Lwin, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Fritz C. Eilber, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

William B. Coley developed bacterial therapy of cancer more than 100 years ago and had clinical success. James Ewing, a very famous cancer pathologist for whom the Ewing sarcoma is named, was Coley's boss at Memorial Hospital in New York and terminated Coley's bacterial therapy of cancer. A tumor from a patient with soft-tissue Ewing's sarcoma, who failed doxorubicin (DOX) therapy, was previously implanted in nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the Ewing's sarcoma PDOX was treated with tumor-targeting S. typhimurium A1-R expressing green fluorescent (GFP), alone and in combination with DOX. S. typhimurium A1-R-GFP was detected in the tumors after intratumor (i.t.) or intravenous (i.v.) injection. The combination of S. typhimurium A1-R and DOX significantly reduced tumor weight (37.8 ± 15.6 mg) compared to the untreated control (73.8 ± 10.1 mg, P < 0.01). S. typhimurium A1-R monotherapy-treated tumors tended to be smaller (50.9 ± 17.8 mg, P = 0.051). DOX monotherapy did not show efficacy (66.3 ± 26.4 mg, P = 0.82), as was the case with the patient. The PDOX model faithfully replicated the DOX resistance the Ewing's sarcoma had in the patient. S. typhimurium A1-R converted the Ewing's sarcoma from DOX resistant to sensitive. One can only wonder how bacterial therapy and immunotherapy of cancer would have developed over the past 80 years if Ewing did not stop Coley.

Original languageEnglish
Pages (from-to)1046-1052
Number of pages7
JournalCell Cycle
Volume16
Issue number11
DOIs
Publication statusPublished - 2017 Jun 3
Externally publishedYes

Keywords

  • Ewing's sarcoma
  • PDOX
  • Salmonella typhimurium A1-R
  • bacterial therapy of cancer
  • patient-derived orthotopic xenograft

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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