Cell mass-dependent expression of an anticancer protein drug by tumor-targeted Salmonella

Kwangsoo Kim, Sa Young Min, Ho Dong Lim, Sung Hwan You, Daejin Lim, Jae Ho Jeong, Hyun Ju Kim, Joon Haeng Rhee, Kyeongil Park, Minsang Shin, Geun Joong Kim, Jung Joon Min, Hyon E. Choy

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Bacterial cancer therapy relies on the properties of certain bacterial species capable of targeting and proliferating within solid malignancies. If these bacteria could be loaded with antitumor proteins, the efficacy of this approach could be greatly increased. However, because most antitumor proteins are also toxic to normal tissue, they must be expressed by bacteria that specifically target and exclusively localize to tumor tissue. As a strategy for treating solid malignancies, we recently evaluated L-asparaginase (L-ASNase) delivered by tumor-targeted Salmonella. In this system, L-ASNase was expressed under the control of the araBAD promoter (PBAD) of the E. coli arabinose operon, which is induced by injection of L-arabinose. Here, we further improved the performance of recombinant Salmonella in cancer therapy by exploiting the quorum-sensing (QS) system, which uses cell mass-dependent auto-induction logic. This approach obviates the necessity of monitoring intratumoral bacterial status and inducing cargo protein expression by administration of an exogenous compound. Recombinant Salmonella in tumors expressed and secreted active L-ASNase in a cell mass-dependent manner, yielding significant anticancer effects. These results suggest that expression of a therapeutic protein under the control of the QS system represents a promising engineering platform for the production of recombinant proteins in vivo.

Original languageEnglish
Pages (from-to)8548-8559
Number of pages12
JournalOncotarget
Volume9
Issue number9
DOIs
StatePublished - 2018

Keywords

  • Bacterial cancer therapy
  • L-asparaginase
  • Quorum-sensing system
  • Salmonella

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