Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models

Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyake, Arun S. Singh, Mark A. Eckardt, Scott D. Nelson, Tara A. Russell, Sarah M. Dry, Yunfeng Li, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Shree Ram Singh, Fritz C. Eilber, Robert M. Hoffman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models. One USS model and one UPS model were doxorubicin (DOX) resistant. One UPS and the NOS model were partially sensitive to DOX. DOX is first-line therapy for these diseases. S. typhimurium A1-R arrested tumor growth all 4 models. In addition to arresting tumor growth in each case, S. typhimurium A1-R was significantly more efficacious than DOX in each case, thereby surpassing first-line therapy. These results suggest that S. typhimurium A1-R can be a general therapeutic for USTS and possibly sarcoma in general.

Original languageEnglish
Pages (from-to)1055-1061
Number of pages7
JournalBiochemical and biophysical research communications
Volume497
Issue number4
DOIs
Publication statusPublished - 2018 Mar 18
Externally publishedYes

Keywords

  • Drug resistant
  • Efficacy
  • PDOX
  • Salmonella typhimurium A1-R
  • Soft-tissue sarcoma
  • Tumor-targeting

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Igarashi, K., Kawaguchi, K., Kiyuna, T., Miyake, K., Miyake, M., Singh, A. S., Eckardt, M. A., Nelson, S. D., Russell, T. A., Dry, S. M., Li, Y., Yamamoto, N., Hayashi, K., Kimura, H., Miwa, S., Tsuchiya, H., Singh, S. R., Eilber, F. C., & Hoffman, R. M. (2018). Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models. Biochemical and biophysical research communications, 497(4), 1055-1061. https://doi.org/10.1016/j.bbrc.2018.02.174