Cell mass-dependent expression of an anticancer protein drug by tumor-targeted Salmonella
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Kwangsoo Kim1,2,*, Sa-Young Min4,*, Ho-Dong Lim4, Sung-Hwan You4, Daejin Lim1,2, Jae-Ho Jeong1,2, Hyun-Ju Kim1,2, Joon Haeng Rhee1,2, Kyeongil Park1,2, Minsang Shin5, Geun-Joong Kim4, Jung-Joon Min2,3 and Hyon E. Choy1,2
1Department of Microbiology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
2Molecular Medicine, BK21 plus, Chonnam National University Graduate School, Gwangju, Republic of Korea
3Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Jeonnam, Republic of Korea
4Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju, Republic of Korea
5Department of Microbiology, Kyungpook National University Medical School, Daegu, Republic of Korea
*These authors contributed equally to this work
Hyon E. Choy, email: firstname.lastname@example.org
Jung-Joon Min, email: email@example.com
Geun-Joong Kim, email: firstname.lastname@example.org
Keywords: bacterial cancer therapy; salmonella; quorum-sensing system; L-asparaginase
Received: August 31, 2017 Accepted: December 03, 2017 Published: January 05, 2018
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.
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