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Nuclear Medicine and Molecular Imaging
Published in: Nuclear Medicine and Molecular Imaging 2/2017

01-06-2017 | Review

Salmonella-Mediated Cancer Therapy: Roles and Potential

Authors: Vu Hong Nguyen, Jung-Joon Min

Published in: Nuclear Medicine and Molecular Imaging | Issue 2/2017

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Abstract

The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT.2.
Literature
1.
2.
McCarthy EF. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J. 2006;26:154–58.PubMedPubMedCentral
3.
Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004;4:437–47.CrossRefPubMed
4.
Fujimori M. Genetically engineered Bifidobacterium as a drug delivery system for systemic therapy of metastatic breast cancer patients. Breast Cancer. 2006;13:27–31.CrossRefPubMed
5.
Hu B, Kou L, Li C, Zhu LP, Fan YR, Wu ZW, et al. Bifidobacterium longum as a delivery system of TRAIL and endostatin cooperates with chemotherapeutic drugs to inhibit hypoxic tumor growth. Cancer Gene Ther. 2009;16:655–63.CrossRefPubMed
6.
Li B, He H, Zhang S, Zhao W, Li N, Shao R. Salmonella typhimurium strain SL7207 induces apoptosis and inhibits the growth of HepG2 hepatoma cells in vitro and in vivo. Acta Pharm Sin B. 2012;2:562–68.CrossRef
7.
Nguyen VH, Kim HS, Ha JM, Hong YJ, Choy HE, Min JJ. Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer. Cancer Res. 2010;70:18–23.CrossRefPubMed
8.
Zhao M, Geller J, Ma H, Yang M, Penman S, Hoffman RM. Monotherapy with a tumor-targeting mutant of Salmonella typhimurium cures orthotopic metastatic mouse models of human prostate cancer. Proc Natl Acad Sci U S A. 2007;104:10170–4.CrossRefPubMedPubMedCentral
9.
Guo H, Zhang J, Inal C, Nguyen T, Fruehauf JH, Keates AC, et al. Targeting tumor gene by shRNA-expressing Salmonella -mediated RNAi. Gene Ther. 2011;18:95–105.CrossRefPubMed
10.
Jeong JH, Kim K, Lim D, Jeong K, Hong Y, Nguyen VH, et al. Anti-tumoral effect of the mitochondrial target domain of Noxa delivered by an engineered Salmonella typhimurium. PLoS ONE. 2014;9:e80050.CrossRefPubMedPubMedCentral
11.
Ryan RM, Green J, Williams PJ, Tazzyman S, Hunt S, Harmey JH, et al. Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors. Gene Ther. 2009;16:329–39.CrossRefPubMed
12.
Ganai S, Arenas RB, Forbes NS. Tumour-targeted delivery of TRAIL using Salmonella typhimurium enhances breast cancer survival in mice. Br J Cancer. 2009;101:1683–91.CrossRefPubMedPubMedCentral
13.
Tang W, He Y, Zhou S, Ma Y, Liu G. A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer. J Exp Clin Cancer Res. 2009;28:155.CrossRefPubMedPubMedCentral
14.
Cronin M, Le Boeuf F, Murphy C, Roy DG, Falls T, Bell JC, et al. Bacterial-mediated knockdown of tumor resistance to an oncolytic virus enhances therapy. Mol Ther. 2014;22:1188–97.CrossRefPubMedPubMedCentral
15.
Lee CH, Wu CL, Tai YS, Shiau AL. Systemic administration of attenuated Salmonella choleraesuis in combination with cisplatin for cancer therapy. Mol Ther. 2005;11:707–16.CrossRefPubMed
16.
Galmbacher K, Heisig M, Hotz C, Wischhusen J, Galmiche A, Bergmann B, et al. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression. PLoS ONE. 2010;5:e9572.CrossRefPubMedPubMedCentral
17.
Roider E, Jellbauer S, Köhn B, Berchtold C, Partilla M, Busch D, et al. Invasion and destruction of a murine fibrosarcoma by Salmonella-induced effector CD8 T cells as a therapeutic intervention against cancer. Cancer Immunol Immunother. 2011;60:371–80.CrossRefPubMed
18.
Lee CH, Wu CL, Shiau AL. Systemic administration of attenuated Salmonella choleraesuis carrying thrombospondin-1 gene leads to tumor-specific transgene expression, delayed tumor growth and prolonged survival in the murine melanoma model. Cancer Gene Ther. 2004;12:175–84.CrossRef
19.
Byrne WL, Murphy CT, Cronin M, Wirth T, Tangney M. Bacterial-mediated DNA delivery to tumour associated phagocytic cells. J Control Release. 2014;196:384–93.CrossRefPubMed
20.
Chen J, Yang B, Cheng X, Qiao Y, Tang B, Chen G, et al. Salmonella-mediated tumor-targeting TRAIL gene therapy significantly suppresses melanoma growth in mouse model. Cancer Sci. 2012;103:325–33.CrossRefPubMed
21.
Quispe-Tintaya W, Chandra D, Jahangir A, Harris M, Casadevall A, Dadachova E, et al. Nontoxic radioactive Listeria at is a highly effective therapy against metastatic pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110:8668–73.CrossRefPubMedPubMedCentral
22.
Kaimala S, Mohamed Y, Nader N, Issac J, Elkord E, Chouaib S, et al. Salmonella-mediated tumor regression involves targeting of tumor myeloid suppressor cells causing a shift to M1-like phenotype and reduction in suppressive capacity. Cancer Immunol Immunother. 2014;63:587–99.CrossRefPubMed
23.
Kim SH, Castro F, Paterson Y, Gravekamp C. High efficacy of a listeria-based vaccine against metastatic breast cancer reveals a dual mode of action. Cancer Res. 2009;69:5860–66.CrossRefPubMedPubMedCentral
24.
Hong EH, Chang SY, Lee BR, Pyun AR, Kim JW, Kweon MN, et al. Intratumoral injection of attenuated Salmonella vaccine can induce tumor microenvironmental shift from immune suppressive to immunogenic. Vaccine. 2013;31:1377–84.CrossRefPubMed
25.
26.
Zhang L, Gao L, Zhao L, Guo B, Ji K, Tian Y, et al. Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhimurium carrying plasmid-based small interfering RNAs. Cancer Res. 2007;67:5859–64.CrossRefPubMed
27.
Saccheri F, Pozzi C, Avogadri F, Barozzi S, Faretta M, Fusi P, et al. Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity. Sci Transl Med. 2010;2:44ra57.CrossRefPubMed
28.
Yang N, Zhu X, Chen L, Li S, Ren D. Oral administration of attenuated S. typhimurium carrying shRNA-expressing vectors as a cancer therapeutic. Cancer Biol Ther. 2008;7:145–51.CrossRefPubMed
29.
Urashima M, Suzuki H, Yuza Y, Akiyama M, Ohno N, Eto Y. An oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium. Blood. 2000;95:1258–63.PubMed
30.
Jiang SN, Park SH, Lee HJ, Zheng JH, Kim HS, Bom HS, et al. Engineering of bacteria for the visualization of targeted delivery of a cytolytic anticancer agent. Mol Ther. 2013;21:1985–95.CrossRefPubMedPubMedCentral
31.
Jiang SN, Phan TX, Nam TK, Nguyen VH, Kim HS, Bom HS, et al. Inhibition of tumor growth and metastasis by a combination of Escherichia coli-mediated cytolytic therapy and radiotherapy. Mol Ther. 2010;18:635–42.CrossRefPubMedPubMedCentral
32.
Jia LJ, Xu HM, Ma DY, Hu QG, Huang XF, Jiang WH, et al. Enhanced therapeutic effect by combination of tumor-targeting salmonella and endostatin in murine melanoma model. Cancer Biol Ther. 2005;4:840–45.CrossRefPubMed
33.
Nishikawa H, Sato E, Briones G, Chen L-M, Matsuo M, Nagata Y, et al. In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines. J Clin Invest. 2006;116:1946–54.CrossRefPubMedPubMedCentral
34.
Min JJ, Nguyen VH, Kim HJ, Hong YJ, Choy HE. Quantitative bioluminescence imaging of tumor-targeting bacteria in living animals. Nat Protoc. 2008;3:629–36.CrossRefPubMed
35.
Min JJ, Kim HJ, Park JH, Moon S, Jeong JH, Hong YJ, et al. Noninvasive real-time imaging of tumors and metastases using tumor-targeting light-emitting Escherichia coli. Mol Imaging Biol. 2008;10:54–61.CrossRefPubMed
36.
37.
Yun M, Pan SO, Jiang S-N, Nguyen VH, Park S-H, Jung C-H, et al. Effect of Salmonella treatment on an implanted tumor (CT26) in a mouse model. J Microbiol. 2012;50:502–10.CrossRefPubMed
38.
Hill PJ, Stritzker J, Scadeng M, Geissinger U, Haddad D, Basse-Lüsebrink TC, et al. Magnetic resonance imaging of tumors colonized with bacterial ferritin-expressing Escherichia coli. PLoS ONE. 2011;6:e25409.CrossRefPubMedPubMedCentral
39.
Soghomonyan SA, Doubrovin M, Pike J, Luo X, Ittensohn M, Runyan JD, et al. Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK. Cancer Gene Ther. 2004;12:101–08.CrossRef
40.
41.
42.
Lambin P, Theys J, Landuyt W, Rijken P, van der Kogel A, van der Schueren E, et al. Colonisation of Clostridium in the body is restricted to hypoxic and necrotic areas of tumours. Anaerobe. 1998;4:183–88.CrossRefPubMed
43.
Yazawa K, Fujimori M, Amano J, Kano Y, Taniguchi S. Bifidobacterium longum as a delivery system for cancer gene therapy: Selective localization and growth in hypoxic tumors. Cancer Gene Ther. 2000;7:269–74.CrossRefPubMed
44.
45.
Toley BJ, Forbes NS. Motility is critical for effective distribution and accumulation of bacteria in tumor tissue. Integr Biol. 2012;4:165–76.CrossRef
46.
Ganai S, Arenas RB, Sauer JP, Bentley B, Forbes NS. In tumors Salmonella migrate away from vasculature toward the transition zone and induce apoptosis. Cancer Gene Ther. 2011;18:457–66.CrossRefPubMedPubMedCentral
47.
Kasinskas RW, Forbes NS. Salmonella typhimurium lacking ribose chemoreceptors localize in tumor quiescence and induce apoptosis. Cancer Res. 2007;67:3201–09.CrossRefPubMed
48.
Leschner S, Westphal K, Dietrich N, Viegas N, Jablonska J, Lyszkiewicz M, et al. Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-alpha. PLoS One. 2009;4:e6692.CrossRefPubMedPubMedCentral
49.
Crull K, Bumann D, Weiss S. Influence of infection route and virulence factors on colonization of solid tumors by Salmonella enterica serovar Typhimurium. FEMS Immunol Med Microbiol. 2011;62:75–83.CrossRefPubMed
50.
Igney FH, Krammer PH. Immune escape of tumors: apoptosis resistance and tumor counterattack. J Leukoc Biol. 2002;71:907–20.PubMed
51.
Westphal K, Leschner S, Jablonska J, Loessner H, Weiss S. Containment of tumor-colonizing bacteria by host neutrophils. Cancer Res. 2008;68:2952–60.CrossRefPubMed
52.
Allport JR, Weissleder R. In vivo imaging of gene and cell therapies. Exp Hematol. 2001;29:1237–46.CrossRefPubMed
53.
Wu JC, Sundaresan G, Iyer M, Gambhir SS. Noninvasive optical imaging of firefly luciferase reporter gene expression in skeletal muscles of living mice. Mol Ther. 2001;4:297–306.CrossRefPubMed
54.
Min JJ, Nguyen VH, Gambhir SS. Molecular imaging of biological gene delivery vehicles for targeted cancer therapy: beyond viral vectors. Nucl Med Mol Imaging. 2010;44:15–24.CrossRefPubMedPubMedCentral
55.
Zhao M, Yang M, Li XM, Jiang P, Baranov E, Li S, et al. Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. Proc Natl Acad Sci U S A. 2005;102:755–60.CrossRefPubMedPubMedCentral
56.
Yang M, Baranov E, Moossa A, Penman S, Hoffman M. Visualizing gene expression by whole-body fluorescence imaging. Proc Natl Acad Sci U S A. 2000;97:12278–82.CrossRefPubMedPubMedCentral
57.
Ntziachristos V, Ripoll J, Wang LV, Weissleder R. Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotechnol. 2005;23:313–20.CrossRefPubMed
58.
Shaner NC, Steinbach PA, Tsien RY. A guide to choosing fluorescent proteins. Nat Methods. 2005;2:905–09.CrossRefPubMed
59.
Ntziachristos V, Tung CH, Bremer C, Weissleder R. Fluorescence molecular tomography resolves protease activity in vivo. Nat Med. 2002;8:757–61.CrossRefPubMed
60.
Danino T, Prindle A, Kwong GA, Skalak M, Li H, Allen K, et al. Programmable probiotics for detection of cancer in urine. Sci Transl Med. 2015;7:289ra84–89ra84.CrossRefPubMedPubMedCentral
61.
Na HS, Kim HJ, Lee HC, Hong Y, Rhee JH, Choy HE. Immune response induced by Salmonella typhimurium defective in ppGpp synthesis. Vaccine. 2006;24:2027–34.CrossRefPubMed
62.
Nemunaitis J, Cunningham C, Senzer N, Kuhn J, Cramm J, Litz C, et al. Pilot trial of genetically modified, attenuated Salmonella expressing the E. coli cytosine deaminase gene in refractory cancer patients. Cancer Gene Ther. 2003;10:737–44.CrossRefPubMed
63.
Critchley RJ, Jezzard S, Radford KJ, Goussard S, Lemoine NR, Grillot-Courvalin C, et al. Potential therapeutic applications of recombinant, invasive E. coli. Gene Ther. 2004;11:1224–33.CrossRefPubMed
64.
Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2002;2:420–30.CrossRefPubMed
65.
Lemmon MJ, van Zijl P, Fox ME, Mauchline ML, Giaccia AJ, Minton NP, et al. Anaerobic bacteria as a gene delivery system that is controlled by the tumor microenvironment. Gene Ther. 1997;4:791–96.CrossRefPubMed
66.
Fox ME, Lemmon MJ, Mauchline ML, Davis TO, Giaccia AJ, Minton NP, et al. Anaerobic bacteria as a delivery system for cancer gene therapy: in vitro activation of 5-fluorocytosine by genetically engineered clostridia. Gene Ther. 1996;3:173–78.PubMed
67.
Munn DH, Mellor AL. The tumor-draining lymph node as an immune-privileged site. Immunol Rev. 2006;213:146–58.CrossRefPubMed
68.
Weibel S, Stritzker J, Eck M, Goebel W, Szalay AA. Colonization of experimental murine breast tumours by Escherichia coli K-12 significantly alters the tumour microenvironment. Cell Microbiol. 2008;10:1235–48.CrossRefPubMed
69.
Quatromoni JG, Eruslanov E. Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer. Am J Transl Res. 2012;4:376–89.PubMedPubMedCentral
70.
Platt J, Sodi S, Kelley M, Rockwell S, Bermudes D, Low KB, et al. Antitumour effects of genetically engineered Salmonella in combination with radiation. Eur J Cancer. 2000;36:2397–402.CrossRefPubMed
71.
Hong H, Lim D, Kim GJ, Park SH, Sik Kim H, Hong Y, et al. Targeted deletion of the ara operon of Salmonella typhimurium enhances L-arabinose accumulation and drives pBAD-promoted expression of anti-cancer toxins and imaging agents. Cell Cycle. 2014;13:3112–20.CrossRefPubMedPubMedCentral
72.
Anderson JC, Clarke EJ, Arkin AP, Voigt CA. Environmentally controlled invasion of cancer cells by engineered bacteria. J Mol Biol. 2006;355:619–27.CrossRefPubMed
73.
Dai Y, Toley BJ, Swofford CA, Forbes NS. Construction of an inducible cell-communication system that amplifies Salmonella gene expression in tumor tissue. Biotechnol Bioeng. 2013;110:1769–81.CrossRefPubMed
74.
Leschner S, Deyneko IV, Lienenklaus S, Wolf K, Bloecker H, Bumann D, et al. Identification of tumor-specific Salmonella typhimurium promoters and their regulatory logic. Nucleic Acids Res. 2012;40:2984–94.CrossRefPubMed
75.
Mengesha A, Dubois L, Lambin P, Landuyt W, Chiu RK, Wouters BG, et al. Development of a flexible and potent hypoxia-inducible promoter for tumor-targeted gene expression in attenuated salmonella. Cancer Biol Ther. 2006;5:1120–28.CrossRefPubMed
76.
77.
Baron U, Freundlieb S, Gossen M, Bujard H. Co-regulation of two gene activities by tetracycline via a bidirectional promoter. Nucleic Acids Res. 1995;23:3605–06.CrossRefPubMedPubMedCentral
78.
Anderson DG, Kowalczykowski SC. Reconstitution of an SOS response pathway: derepression of transcription in response to DNA breaks. Cell. 1998;95:975–79.CrossRefPubMed
79.
Mengesha A, Dubois L, Lambin P, Landuyt W, Chiu R, Wouters B, et al. Development of a flexible and potent hypoxia-inducible promoter for tumor-targeted gene expression in attenuated Salmonella. Cancer Biol Ther. 2006;5:1120–8.CrossRefPubMed
Metadata
Title
Salmonella-Mediated Cancer Therapy: Roles and Potential
Authors
Vu Hong Nguyen
Jung-Joon Min
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
Nuclear Medicine and Molecular Imaging / Issue 2/2017
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-016-0415-z

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