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

Oncotarget
Kwangsoo KimHyon E Choy

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 ...Continue Reading

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Citations

Oct 18, 2020·International Journal of Molecular Sciences·Shruti S SawantNitesh K Kunda
Oct 11, 2020·Biotechnology and Bioengineering·Kang LiangQingke Kong
Dec 13, 2019·Experimental & Molecular Medicine·Mai Thi-Quynh DuongJung-Joon Min
Dec 12, 2020·Trends in Cancer·Brendan Fu-Long SieowMatthew Wook Chang

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Methods Mentioned

BETA
xenograft
deamination
PCR
fluorescence microscopy
enzyme-linked immunosorbent assay
electrophoresis
Assay

Software Mentioned

pQSI
ASN
pQSR
SPSS
Mock

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