Skip to main content
Log in

Salmonella—allies in the fight against cancer

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Cancer has become the second ranking cause of death in the industrialized world. Conventional anti-cancer therapies such as surgery, radiotherapy, and chemotherapy are effective in the treatment of solid tumors only to some extent. Furthermore, they are often associated with severe side effects. Use of bacteria as alternative cancer therapeutics has sporadically been followed over more than a century. The potential to target and colonize solid tumors could be shown for many different bacteria in the meantime. Such bacteria are either obligate anaerobic bacteria like Clostridium or Bifidobacterium or facultative anaerobic like Escherichia coli or Salmonella. Here we describe bacterial strains that were successfully applied mostly in animals bearing model tumors, although first clinical trials have been reported as well. Our review mainly concentrates on Salmonella enterica serovar Typhimurium (S. Typhimurium) since these bacteria were studied most intensively thus far. Importantly, S. Typhimurium were shown not only to colonize large established tumors but also exhibit the property to invade and affect metastases. We report on a potential mechanism by which such bacteria can invade solid tumors. Furthermore, we describe several successful attempts in which the bacteria have been used as carriers for recombinant therapeutic molecules that render bacteria more powerful in eradication of the established tumor. Such attempts should be considered starting points on the way to an effective and safe tumor therapy with the help of bacteria.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Barbe S, Van Mellaert L, Anne J (2006) The use of clostridial spores for cancer treatment. J Appl Microbiol 101:571–578

    Article  CAS  PubMed  Google Scholar 

  2. Pawelek JM, Low KB, Bermudes D (2003) Bacteria as tumour-targeting vectors. Lancet Oncol 4:548–556

    Article  PubMed  Google Scholar 

  3. Busch W (1868) Verhandlungen ärztlicher Gesellschaften. Berliner Klinische Wochenschrift 187–189

  4. Coley WB (1991) The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res 3–11

  5. Minton NP (2003) Clostridia in cancer therapy. Nat Rev Microbiol 1:237–242

    Article  CAS  PubMed  Google Scholar 

  6. Theys J, Barbe S, Landuyt W, Nuyts S, Van Mellaert L, Wouters B, Anne J, Lambin P (2003) Tumor-specific gene delivery using genetically engineered bacteria. Curr Gene Ther 3:207–221

    Article  CAS  PubMed  Google Scholar 

  7. Akaza H (1995) BCG treatment of existing Ta, T1 tumours or carcinoma in situ of the bladder. Eur Urol 27(Suppl 1):9–12

    PubMed  Google Scholar 

  8. Van Mellaert L, Barbe S, Anne J (2006) Clostridium spores as anti-tumour agents. Trends Microbiol 14:190–196

    Article  PubMed  Google Scholar 

  9. Dang LH, Bettegowda C, Huso DL, Kinzler KW, Vogelstein B (2001) Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci U S A 98:15155–15160

    Article  CAS  PubMed  Google Scholar 

  10. Bettegowda C, Dang LH, Abrams R, Huso DL, Dillehay L, Cheong I, Agrawal N, Borzillary S, McCaffery JM, Watson EL et al (2003) Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria. Proc Natl Acad Sci U S A 100:15083–15088

    Article  CAS  PubMed  Google Scholar 

  11. Cheong I, Huang X, Bettegowda C, Diaz LA Jr, Kinzler KW, Zhou S, Vogelstein B (2006) A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science 314:1308–1311

    Article  CAS  PubMed  Google Scholar 

  12. Hidaka A, Hamaji Y, Sasaki T, Taniguchi S, Fujimori M (2007) Exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy. Biosci Biotechnol Biochem 71:2921–2926

    Article  CAS  PubMed  Google Scholar 

  13. Sasaki T, Fujimori M, Hamaji Y, Hama Y, Ito K, Amano J, Taniguchi S (2006) Genetically engineered Bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats. Cancer Sci 97:649–657

    Article  CAS  PubMed  Google Scholar 

  14. Xu YF, Zhu LP, Hu B, Fu GF, Zhang HY, Wang JJ, Xu GX (2007) A new expression plasmid in Bifidobacterium longum as a delivery system of endostatin for cancer gene therapy. Cancer Gene Ther 14:151–157

    Article  CAS  PubMed  Google Scholar 

  15. Zhu LP, Yin Y, Xing J, Li C, Kou L, Hu B, Wu ZW, Wang JJ, Xu GX (2009) Therapeutic efficacy of Bifidobacterium longum-mediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors. Cancer Sci 100:1986–1990

    Article  CAS  PubMed  Google Scholar 

  16. Hu B, Kou L, Li C, Zhu LP, Fan YR, Wu ZW, Wang JJ, Xu GX (2009) Bifidobacterium longum as a delivery system of TRAIL and endostatin cooperates with chemotherapeutic drugs to inhibit hypoxic tumor growth. Cancer Gene Ther 16:655–663

    Article  CAS  PubMed  Google Scholar 

  17. Yazawa K, Fujimori M, Nakamura T, Sasaki T, Amano J, Kano Y, Taniguchi S (2001) Bifidobacterium longum as a delivery system for gene therapy of chemically induced rat mammary tumors. Breast Cancer Res Treat 66:165–170

    Article  CAS  PubMed  Google Scholar 

  18. Folkman J (2006) Antiangiogenesis in cancer therapy—endostatin and its mechanisms of action. Exp Cell Res 312:594–607

    Article  CAS  PubMed  Google Scholar 

  19. Li X, Fu GF, Fan YR, Liu WH, Liu XJ, Wang JJ, Xu GX (2003) Bifidobacterium adolescentis as a delivery system of endostatin for cancer gene therapy: selective inhibitor of angiogenesis and hypoxic tumor growth. Cancer Gene Ther 10:105–111

    Article  CAS  PubMed  Google Scholar 

  20. Scott MT (1972) Biological effects of the adjuvant Corynebacterium parvum. I. Inhibition of PHA, mixed lymphocyte and GVH reactivity. Cell Immunol 5:459–468

    Article  CAS  PubMed  Google Scholar 

  21. Woodruff MF, McBride WH, Dunbar N (1974) Tumour growth, phagocytic activity and antibody response in Corynebacterium parvum-treated mice. Clin Exp Immunol 17:509–518

    CAS  PubMed  Google Scholar 

  22. Fisher B, Brown A, Wolmark N, Fisher ER, Redmond C, Wickerham DL, Margolese R, Dimitrov N, Pilch Y, Glass A et al (1990) Evaluation of the worth of Corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer. Eight-year results from the National Surgical Adjuvant Breast and Bowel Project B-10. Cancer 66:220–227

    Article  CAS  PubMed  Google Scholar 

  23. Currie GA (1970) Active immunotherapy with Corynebacterium parvum and chemotherapy in murine fibrosarcomas. Br Med J 1:541–544

    Article  CAS  PubMed  Google Scholar 

  24. Fisher B, Wolmark N, Saffer E, Fisher ER (1975) Inhibitory effect of prolonged Corynebacterium parvum and cyclophosphamide administration on the growth of established tumors. Cancer 35:134–143

    Article  CAS  PubMed  Google Scholar 

  25. Fisher B, Rubin H, Sartiano G, Ennis L, Wolmark N (1976) Observations following Corynebacterium parvum administration to patients with advanced malignancy. A phase I study. Cancer 38:119–130

    Article  CAS  PubMed  Google Scholar 

  26. Yu YA, Shabahang S, Timiryasova TM, Zhang Q, Beltz R, Gentschev I, Goebel W, Szalay AA (2004) Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins. Nat Biotechnol 22:313–320

    Article  CAS  PubMed  Google Scholar 

  27. Yu YA, Zhang Q, Szalay AA (2008) Establishment and characterization of conditions required for tumor colonization by intravenously delivered bacteria. Biotechnol Bioeng 100:567–578

    Article  CAS  PubMed  Google Scholar 

  28. Stritzker J, Weibel S, Hill PJ, Oelschlaeger TA, Goebel W, Szalay AA (2007) Tumor-specific colonization, tissue distribution, and gene induction by probiotic Escherichia coli Nissle 1917 in live mice. Int J Med Microbiol 297:151–162

    Article  CAS  PubMed  Google Scholar 

  29. Cheng CM, Lu YL, Chuang KH, Hung WC, Shiea J, Su YC, Kao CH, Chen BM, Roffler S, Cheng TL (2008) Tumor-targeting prodrug-activating bacteria for cancer therapy. Cancer Gene Ther 15:393–401

    Article  CAS  PubMed  Google Scholar 

  30. Xiang S, Fruehauf J, Li CJ (2006) Short hairpin RNA-expressing bacteria elicit RNA interference in mammals. Nat Biotechnol 24:697–702

    Article  CAS  PubMed  Google Scholar 

  31. Brader P, Stritzker J, Riedl CC, Zanzonico P, Cai S, Burnazi EM, Ghani ER, Hricak H, Szalay AA, Fong Y et al (2008) Escherichia coli Nissle 1917 facilitates tumor detection by positron emission tomography and optical imaging. Clin Cancer Res 14:2295–2302

    Article  CAS  PubMed  Google Scholar 

  32. Weibel S, Stritzker J, Eck M, Goebel W, Szalay AA (2008) Colonization of experimental murine breast tumours by Escherichia coli K-12 significantly alters the tumour microenvironment. Cell Microbiol 10:1235–1248

    Article  CAS  PubMed  Google Scholar 

  33. Pawelek JM, Low KB, Bermudes D (1997) Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res 57:4537–4544

    CAS  PubMed  Google Scholar 

  34. Yam C, Zhao M, Hayashi K, Ma H, Kishimoto H, McElroy M, Bouvet M, Hoffman RM (2009) Monotherapy with a tumor-targeting mutant of S. typhimurium Inhibits Liver Metastasis in a Mouse Model of Pancreatic Cancer. J Surg Res [Epub ahead of print]

  35. Low KB, Ittensohn M, Le T, Platt J, Sodi S, Amoss M, Ash O, Carmichael E, Chakraborty A, Fischer J et al (1999) Lipid A mutant Salmonella with suppressed virulence and TNFalpha induction retain tumor-targeting in vivo. Nat Biotechnol 17:37–41

    CAS  PubMed  Google Scholar 

  36. Toso JF, Gill VJ, Hwu P, Marincola FM, Restifo NP, Schwartzentruber DJ, Sherry RM, Topalian SL, Yang JC, Stock F et al (2002) Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J Clin Oncol 20:142–152

    Article  PubMed  Google Scholar 

  37. Heimann DM, Rosenberg SA (2003) Continuous intravenous administration of live genetically modified salmonella typhimurium in patients with metastatic melanoma. J Immunother 26:179–180

    Article  PubMed  Google Scholar 

  38. Kasinskas RW, Forbes NS (2006) Salmonella typhimurium specifically chemotax and proliferate in heterogeneous tumor tissue in vitro. Biotechnol Bioeng 94:710–721

    Article  CAS  PubMed  Google Scholar 

  39. Kasinskas RW, Forbes NS (2007) Salmonella typhimurium lacking ribose chemoreceptors localize in tumor quiescence and induce apoptosis. Cancer Res 67:3201–3209

    Article  CAS  PubMed  Google Scholar 

  40. Leschner S, Westphal K, Dietrich N, Viegas N, Jablonska J, Lyszkiewicz M, Lienenklaus S, Falk W, Gekara N, Loessner H et al (2009) Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-alpha. PLoS One 4:e6692

    Article  PubMed  Google Scholar 

  41. King I, Bermudes D, Lin S, Belcourt M, Pike J, Troy K, Le T, Ittensohn M, Mao J, Lang W et al (2002) Tumor-targeted Salmonella expressing cytosine deaminase as an anticancer agent. Hum Gene Ther 13:1225–1233

    Article  CAS  PubMed  Google Scholar 

  42. Nemunaitis J, Cunningham C, Senzer N, Kuhn J, Cramm J, Litz C, Cavagnolo R, Cahill A, Clairmont C, Sznol M (2003) Pilot trial of genetically modified, attenuated Salmonella expressing the E. coli cytosine deaminase gene in refractory cancer patients. Cancer Gene Ther 10:737–744

    Article  CAS  PubMed  Google Scholar 

  43. Royo JL, Becker PD, Camacho EM, Cebolla A, Link C, Santero E, Guzman CA (2007) In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit. Nat Meth 4:937–942

    Article  CAS  Google Scholar 

  44. Friedlos F, Lehouritis P, Ogilvie L, Hedley D, Davies L, Bermudes D, King I, Martin J, Marais R, Springer CJ (2008) Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy. Clin Cancer Res 14:4259–4266

    Article  CAS  PubMed  Google Scholar 

  45. Saltzman DA, Heise CP, Hasz DE, Zebede M, Kelly SM, Curtiss R III, Leonard AS, Anderson PM (1996) Attenuated Salmonella typhimurium containing interleukin-2 decreases MC-38 hepatic metastases: a novel anti-tumor agent. Cancer Biother Radiopharm 11:145–153

    Article  CAS  PubMed  Google Scholar 

  46. Saltzman DA, Katsanis E, Heise CP, Hasz DE, Vigdorovich V, Kelly SM, Curtiss R III, Leonard AS, Anderson PM (1997) Antitumor mechanisms of attenuated Salmonella typhimurium containing the gene for human interleukin-2: a novel antitumor agent? J Pediatr Surg 32:301–306

    Article  CAS  PubMed  Google Scholar 

  47. Sorenson BS, Banton KL, Frykman NL, Leonard AS, Saltzman DA (2008) Attenuated Salmonella typhimurium with IL-2 gene reduces pulmonary metastases in murine osteosarcoma. Clin Orthop Relat Res 466:1285–1291

    Article  PubMed  Google Scholar 

  48. Sorenson BS, Banton KL, Frykman NL, Leonard AS, Saltzman DA (2008) Attenuated Salmonella typhimurium with interleukin 2 gene prevents the establishment of pulmonary metastases in a model of osteosarcoma. J Pediatr Surg 43:1153–1158

    Article  PubMed  Google Scholar 

  49. Al Ramadi BK, Fernandez-Cabezudo MJ, El Hasasna H, Al Salam S, Bashir G, Chouaib S (2009) Potent anti-tumor activity of systemically-administered IL2-expressing Salmonella correlates with decreased angiogenesis and enhanced tumor apoptosis. Clin Immunol 130:89–97

    Article  CAS  PubMed  Google Scholar 

  50. Al Ramadi BK, Fernandez-Cabezudo MJ, El Hasasna H, Al Salam S, Attoub S, Xu D, Chouaib S (2008) Attenuated bacteria as effectors in cancer immunotherapy. Ann NY Acad Sci 1138:351–357

    Article  CAS  PubMed  Google Scholar 

  51. Loeffler M, Le'Negrate G, Krajewska M, Reed JC (2008) Inhibition of tumor growth using salmonella expressing Fas ligand. J Natl Cancer Inst 100:1113–1116

    Article  CAS  PubMed  Google Scholar 

  52. Loeffler M, Le'Negrate G, Krajewska M, Reed JC (2008) IL-18-producing Salmonella inhibit tumor growth. Cancer Gene Ther 15:787–794

    Google Scholar 

  53. Loeffler M, Le'Negrate G, Krajewska M, Reed JC (2008) Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth. Cancer Immunol Immunother 58:769–775

    Google Scholar 

  54. Loeffler M, Le'Negrate G, Krajewska M, Reed JC (2007) Attenuated Salmonella engineered to produce human cytokine LIGHT inhibit tumor growth. Proc Natl Acad Sci U S A 104:12879–12883

    Article  CAS  PubMed  Google Scholar 

  55. Lancaster LE, Wintermeyer W, Rodnina MV (2007) Colicins and their potential in cancer treatment. Blood Cells Mol Dis 38:15–18

    Article  CAS  PubMed  Google Scholar 

  56. Ryan RM, Green J, Williams PJ, Tazzyman S, Hunt S, Harmey JH, Kehoe SC, Lewis CE (2009) Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors. Gene Ther 16:329–339

    Article  CAS  PubMed  Google Scholar 

  57. Nguyen VH, Kim HS, Ha JM, Hong Y, Choy HE, Min JJ (2010) Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer. Cancer Res 70:18–23

    Article  CAS  PubMed  Google Scholar 

  58. Weiss S, Chakraborty T (2001) Transfer of eukaryotic expression plasmids to mammalian host cells by bacterial carriers. Curr Opin Biotechnol 12:467–472

    Article  CAS  PubMed  Google Scholar 

  59. Darji A, Guzman CA, Gerstel B, Wachholz P, Timmis KN, Wehland J, Chakraborty T, Weiss S (1997) Oral somatic transgene vaccination using attenuated S. typhimurium. Cell 91:765–775

    Article  CAS  PubMed  Google Scholar 

  60. Lee CH, Wu CL, Shiau AL (2005) 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 12:175–184

    Article  CAS  PubMed  Google Scholar 

  61. Lee CH, Wu CL, Shiau AL (2004) Endostatin gene therapy delivered by Salmonella choleraesuis in murine tumor models. J Gene Med 6:1382–1393

    Article  CAS  PubMed  Google Scholar 

  62. Yoon WS, Choi WC, Sin JI, Park YK (2007) Antitumor therapeutic effects of Salmonella typhimurium containing Flt3 Ligand expression plasmids in melanoma-bearing mouse. Biotechnol Lett 29:511–516

    Article  CAS  PubMed  Google Scholar 

  63. Fu W, Lan H, Li S, Han X, Gao T, Ren D (2008) Synergistic antitumor efficacy of suicide/ePNP gene and 6-methylpurine 2′-deoxyriboside via Salmonella against murine tumors. Cancer Gene Ther 15:474–484

    Article  CAS  PubMed  Google Scholar 

  64. Fu W, Lan H, Liang S, Gao T, Ren D (2008) Suicide gene/prodrug therapy using salmonella-mediated delivery of Escherichia coli purine nucleoside phosphorylase gene and 6-methoxypurine 2′-deoxyriboside in murine mammary carcinoma 4T1 model. Cancer Sci 99:1172–1179

    Article  CAS  PubMed  Google Scholar 

  65. Fu W, Chu L, Han X, Liu X, Ren D (2008) Synergistic antitumoral effects of human telomerase reverse transcriptase-mediated dual-apoptosis-related gene vector delivered by orally attenuated Salmonella enterica serovar Typhimurium in murine tumor models. J Gene Med 10:690–701

    Article  CAS  PubMed  Google Scholar 

  66. Zhang L, Gao L, Zhao L, Guo B, Ji K, Tian Y, Wang J, Yu H, Hu J, Kalvakolanu DV et al (2007) Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhimurium carrying plasmid-based small interfering RNAs. Cancer Res 67:5859–5864

    Article  CAS  PubMed  Google Scholar 

  67. Yang N, Zhu X, Chen L, Li S, Ren D (2008) Oral administration of attenuated S. typhimurium carrying shRNA-expressing vectors as a cancer therapeutic. Cancer Biol Ther 7:145–151

    Article  CAS  PubMed  Google Scholar 

  68. Agorio C, Schreiber F, Sheppard M, Mastroeni P, Fernandez M, Martinez MA, Chabalgoity JA (2007) Live attenuated Salmonella as a vector for oral cytokine gene therapy in melanoma. J Gene Med 9:416–423

    Google Scholar 

  69. Loessner H, Endmann A, Leschner S, Westphal K, Rohde M, Miloud T, Hammerling G, Neuhaus K, Weiss S (2007) Remote control of tumour-targeted Salmonella enterica serovar Typhimurium by the use of L-arabinose as inducer of bacterial gene expression in vivo. Cell Microbiol 9:1529–1537

    Google Scholar 

  70. Jia LJ, Xu HM, Ma DY, Hu QG, Huang XF, Jiang WH, Li SF, Jia KZ, Huang QL, Hua ZC (2005) Enhanced therapeutic effect by combination of tumor-targeting Salmonella and endostatin in murine melanoma model. Cancer Biol Ther 4:840–845

    CAS  PubMed  Google Scholar 

  71. Jia LJ, Wei DP, Sun QM, Jin GH, Li SF, Huang Y, Hua ZC (2007) Tumor-targeting Salmonella typhimurium improves cyclophosphamide chemotherapy at maximum tolerated dose and low-dose metronomic regimens in a murine melanoma model. Int J Cancer 121:666–674

    Article  CAS  PubMed  Google Scholar 

  72. Lee CH, Wu CL, Tai YS, Shiau AL (2005) Systemic administration of attenuated Salmonella choleraesuis in combination with cisplatin for cancer therapy. Mol Ther 11:707–716

    Article  CAS  PubMed  Google Scholar 

  73. Platt J, Sodi S, Kelley M, Rockwell S, Bermudes D, Low KB, Pawelek J (2000) Antitumour effects of genetically engineered Salmonella in combination with radiation. Eur J Cancer 36:2397–2402

    Article  CAS  PubMed  Google Scholar 

  74. Avogadri F, Mittal D, Saccheri F, Sarrafiore M, Ciocca M, Larghi P, Orecchia R, Rescigno M (2008) Intra-tumoral Salmonella typhimurium induces a systemic anti-tumor immune response that is directed by low-dose radiation to treat distal disease. Eur J Immunol 38:1937–1947

    Article  CAS  PubMed  Google Scholar 

  75. Yuhua L, Kunyuan G, Hui C, Yongmei X, Chaoyang S, Xun T, Daming R (2001) Oral cytokine gene therapy against murine tumor using attenuated Salmonella typhimurium. Int J Cancer 94:438–443

    Article  CAS  PubMed  Google Scholar 

  76. Jia LJ, Wei DP, Sun QM, Huang Y, Wu Q, Hua ZC (2007) Oral delivery of tumor-targeting Salmonella for cancer therapy in murine tumor models. Cancer Sci 98:1107–1112

    Google Scholar 

  77. Chen G, Wei DP, Jia LJ, Tang B, Shu L, Zhang K, Xu Y, Gao J, Huang XF, Jiang WH et al (2009) Oral delivery of tumor-targeting Salmonella exhibits promising therapeutic efficacy and low toxicity. Cancer Sci 100:2437–2443

    Google Scholar 

  78. Westphal K, Leschner S, Jablonska J, Loessner H, Weiss S (2008) Containment of tumor-colonizing bacteria by host neutrophils. Cancer Res 68:2952–2960

    Article  CAS  PubMed  Google Scholar 

  79. Zhao M, Yang M, Li XM, Jiang P, Baranov E, Li S, Xu M, Penman S, Hoffman RM (2005) Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. Proc Natl Acad Sci U S A 102:755–760

    Article  CAS  PubMed  Google Scholar 

  80. Zhao M, Yang M, Ma H, Li X, Tan X, Li S, Yang Z, Hoffman RM (2006) Targeted therapy with a Salmonella typhimurium leucine–arginine auxotroph cures orthotopic human breast tumors in nude mice. Cancer Res 66:7647–7652

    Article  CAS  PubMed  Google Scholar 

  81. Zhao M, Geller J, Ma H, Yang M, Penman S, Hoffman RM (2007) 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 104:10170–10174

    Article  CAS  PubMed  Google Scholar 

  82. Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Kishimoto H, Bouvet M, Hoffman RM (2009) Systemic targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma in nude mice with a tumor-selective strain of Salmonella typhimurium. Cell Cycle 8:870–875

    CAS  PubMed  Google Scholar 

  83. Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Hoffman RM (2009) Cancer metastasis directly eradicated by targeted therapy with a modified Salmonella typhimurium. J Cell Biochem 106:992–998

    Article  CAS  PubMed  Google Scholar 

  84. Nagakura C, Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Bouvet M, Hoffman RM (2009) Efficacy of a genetically-modified Salmonella typhimurium in an orthotopic human pancreatic cancer in nude mice. Anticancer Res 29:1873–1878

    PubMed  Google Scholar 

  85. Kimura H, Zhang L, Zhao M, Hayashi K, Tsuchiya H, Tomita K, Bouvet M, Wessels J, Hoffman RM (2010) Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium. Cell Prolif 43:41–48

    Article  CAS  PubMed  Google Scholar 

  86. Arrach N, Cheng P, Zhao M, Santiviago CA, Hoffman RM, McClelland M (2010) High-throughput screening for salmonella avirulent mutants that retain targeting of solid tumors. Cancer Res 70:2165–2170

    Article  CAS  PubMed  Google Scholar 

  87. Mengesha A, Dubois L, Lambin P, Landuyt W, Chiu RK, Wouters BG, Theys J (2006) Development of a flexible and potent hypoxia-inducible promoter for tumor-targeted gene expression in attenuated Salmonella. Cancer Biol Ther 5:1120–1128

    CAS  PubMed  Google Scholar 

  88. Ryan RM, Green J, Williams PJ, Tazzyman S, Hunt S, Harmey JH, Kehoe SC, Lewis CE (2009) Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors. Gene Ther 16:329–339

    Article  CAS  PubMed  Google Scholar 

  89. Arrach N, Zhao M, Porwollik S, Hoffman RM, McClelland M (2008) Salmonella promoters preferentially activated inside tumors. Cancer Res 68:4827–4832

    Article  CAS  PubMed  Google Scholar 

  90. Loessner H, Leschner S, Endmann A, Westphal K, Wolf K, Kochruebe K, Miloud T, Altenbuchner J, Weiss S (2009) Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice. Microbes Infect 11:1097–1105

    Article  CAS  PubMed  Google Scholar 

Download references

Disclosure statement

The authors declare no conflict of interest related to this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sara Leschner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leschner, S., Weiss, S. Salmonella—allies in the fight against cancer. J Mol Med 88, 763–773 (2010). https://doi.org/10.1007/s00109-010-0636-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-010-0636-z

Keywords

Navigation