Efficacy of Tumor-Targeting Salmonella typhimurium A1-R against Malignancies in Patient-Derived Orthotopic Xenograft (PDOX) Murine Models

Cells. 2019 Jun 16;8(6):599. doi: 10.3390/cells8060599.

Abstract

We developed tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R, a facultative anaerobe that is an auxotroph of leucine and arginine. The tumor-targeting efficacy of S. typhimurium A1-R was demonstrated in vivo and vitro using several malignant cell lines including melanoma, sarcoma, glioma, breast, pancreatic, colon, cervical, prostate, and ovarian cancers. Our laboratory also developed a patient-derived orthotopic xenograft (PDOX) model by implanting patient-derived malignant tumor fragments into orthotopic sites in mice. We reviewed studies of S. typhimurium A1-R against recalcitrant cancers. S. typhimurium A1-R was effective against all PDOX tumor models tested and showed stronger efficacies than chemotherapy or molecular-targeting therapy against some tumors. Furthermore, the synergistic efficacy of S. typhimurium A1-R when combined with chemotherapeutic agents, molecular-targeting agents, or recombinant methioninase was also demonstrated. We suggest potential clinical uses of this S. typhimurium A1-R treatment.

Keywords: Salmonella typhimurium A1-R; bacterial therapy; malignancy; patient-derived orthotopic xenograft; tumor-targeting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Mice
  • Neoplasms / therapy*
  • Salmonella typhimurium / physiology*
  • Xenograft Model Antitumor Assays*