Combination therapy of tumor-targeting Salmonella typhimurium A1-R and oral recombinant methioninase regresses a BRAF-V600E-negative melanoma

Kei Kawaguchi, Takashi Higuchi, Shukuan Li, Qinghong Han, Yuying Tan, Kentaro Igarashi, Ming Zhao, Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Hiromichi Ohshiro, Norihiko Sugisawa, Zhiying Zhang, Sahar Razmjooei, Sintawat Wangsiricharoen, Bartosz Chmielowski, Scott D. Nelson, Tara A. Russell, Sarah M. Dry, Yunfeng LiMark A. Eckardt, Arun S. Singh, Shree Ram Singh, Fritz C. Eilber, Michiaki Unno, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Melanoma is a recalcitrant cancer. To improve and individualize treatment for this disease, we previously developed a patient-derived orthotopic xenograft (PDOX) model for melanoma. We previously reported the individual efficacy of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and recombinant methioninase (rMETase) for melanoma in the PDOX models of this disease. In the present study, we evaluated the efficacy of the combination of S. typhimurium A1-R with orally-administered rMETase (o-rMETase) for BRAF-V600E-negative melanoma in a PDOX model. Three weeks after implantation, 60 PDOX mouse models were randomized into six groups of 10 mice each: untreated control, temozolomide (TEM); o-rMETase; S. typhimurium A1-R; TEM + rMETase, S. typhimurium A1-R + rMETase. All treatments inhibited tumor growth compared to untreated control (TEM: p < 0.0001, rMETase: p < 0.0001, S. typhimurium A1-R: p < 0.0001, TEM + rMETase: p < 0.0001, S. typhimurium A1-R + rMETase: p < 0.0001). The most effective was the combination of S. typhimurium A1-R + o-rMETase which regressed this melanoma PDOX, thereby indicating a new paradigm for treatment of metastatic melanoma.

Original languageEnglish
Pages (from-to)3086-3092
Number of pages7
JournalBiochemical and biophysical research communications
Volume503
Issue number4
DOIs
Publication statusPublished - 2018 Sep 18

Keywords

  • BRAF-V600E-negative melanoma
  • Methionine dependence
  • Nude mice
  • PDOX
  • Precision therapy
  • Recombinant methioninase
  • Salmonella typhimurium A1-R

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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