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.

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.

• Authors: 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
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 16 Issue 11 Pg. 1046-1052 (Jun 03 2017) ISSN: 1551-4005 [Electronic] United States
• PMID: 28296559 (Publication Type: Journal Article)

Chemical References

• Green Fluorescent Proteins
• Doxorubicin

Topics

• Animals
• Doxorubicin (pharmacology, therapeutic use)
• Female
• Green Fluorescent Proteins (metabolism)
• Humans
• Mice
• Mice, Nude
• Middle Aged
• Salmonella typhimurium (physiology)
• Sarcoma, Ewing (drug therapy, pathology, therapy)
• Xenograft Model Antitumor Assays