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Gene Therapy of Solid Cancers pp 239–260Cite as

Back to the Future: Are Tumor-Targeting Bacteria the Next-Generation Cancer Therapy?

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1317))

Abstract

Cancer patients infected with various bacteria were reported, for at least two centuries, to have spontaneous remission. W.B. Coley, of what is now the Memorial Sloan-Kettering Cancer Center, pioneered bacterial therapy of cancer in the clinic with considerable success beginning in the late nineteenth century. After Coley died in 1936, bacterial therapy of cancer essentially ended. Currently there is much excitement in developing bacterial therapy for treating cancer using either obligate or facultative anaerobic bacteria. This chapter will demonstrate the potential and strategy of Salmonella typhimurium A1-R, an engineered tumor-targeting variant for the systemic treatment of metastatic cancer. A new concept using Salmonella typhimurium A1-R for cell cycle “decoy” chemotherapy of metastatic cancer is also described.

The Outsider is … a person who lives on the edge, challenges culture values and ‘stands for truth’. ” Colin Wilson: The Outsider, Tarcher/Penguin, New York, 1982.

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References

  1. Coley W (2013) http://en.wikipedia.org/wiki/William_Coley. Accessed 12 Dec 2013

  2. Forbes NS (2010) Engineering the perfect (bacterial) cancer therapy. Nat Rev Cancer 10:785–794

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Hoption Cann SA, van Netten JP, van Netten C (2003) Dr William Coley and tumour regression: a place in history or in the future. Postgrad Med J 79:672–680

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Richardson MA, Ramirez T, Russell NC, Moye LA (1999) Coley toxins immunotherapy: a retrospective review. Altern Ther Health Med 5:42–47

    CAS  PubMed  Google Scholar 

  5. 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 

  6. 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 Central  PubMed  Google Scholar 

  7. Hoffman RM (2012) Bugging tumors. Cancer Discov 2:588–590

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. Coley WB (1893) The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am J Med Sci 105:487–511

    Article  Google Scholar 

  11. Toso JF, Gill VJ, Hwu P, Marincola FM, Restifo NP, Schwartzentruber DJ, Sherry RM 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 Central  PubMed  Google Scholar 

  12. Hoffman RM (2013) Tumor growth control with IDO-silencing Salmonella (Letter). Cancer Res 73:4591

    Article  CAS  PubMed  Google Scholar 

  13. Blache CA, Manuel ER, Kaltcheva TI, Wong AN, Ellenhorn JD, Blazar BR et al (2012) Systemic delivery of Salmonella typhimurium transformed with IDO shRNA enhances intratumoral vector colonization and suppresses tumor growth. Cancer Res 72:6447–6456

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Manuel ER, Blazer BR, Diamond DJ (2013) Tumor-growth control with IDO-silencing Salmonella (Reply). Cancer Res 73:4592–4593

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Zhao M, Yang M, Li X-M, Jiang P, Baranov E, Li S et al (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 Central  PubMed  Google Scholar 

  16. 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 Central  PubMed  Google Scholar 

  17. Zhao M, Yang M, Ma H, Li X, Tan X, Li S et al (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 

  18. Zhang Y, Tome Y, Suetsugu A, Zhang L, Zhang N, Hoffman RM, Zhao M (2012) Determination of the optimal route of administration of Salmonella typhimurium A1-R to target breast cancer in nude mice. Anticancer Res 32:2501–2508

    PubMed  Google Scholar 

  19. Uchugonova A, Zhao M, Zhang Y, Weinigel M, König K, Hoffman RM (2012) Cancer-cell killing by engineered Salmonella imaged by multiphoton tomography in live mice. Anticancer Res 32:4331–4338

    CAS  PubMed  Google Scholar 

  20. Liu F, Zhang L, Hoffman RM, Zhao M (2010) Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity. Cell Cycle 9:4518–4524

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Nagakura C, Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H et al (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 

  22. Yam C, Zhao M, Hayashi K, Ma H, Kishimoto H, McElroy M et al (2010) Monotherapy with a tumor-targeting mutant of S. typhimurium inhibits liver metastasis in a mouse model of pancreatic cancer. J Surg Res 164:248–255

    Article  PubMed Central  PubMed  Google Scholar 

  23. Hiroshima Y, Zhao M, Zhang Y, Maawy A, Hassanein MK, Uehara F et al (2013) Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells. Cell Cycle 12:2774–2780

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Hiroshima Y, Zhao M, Maawy A, Zhang Y, Katz MH, Fleming JB et al (2014) Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX). J Cell Biochem 115:1254–1261

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K et al (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

    Article  CAS  PubMed  Google Scholar 

  27. Kimura H, Zhang L, Zhao M, Hayashi K, Tsuchiya H, Tomita K et al (2010) Targeted therapy of spinal cord glioma with a genetically-modified Salmonella typhimurium. Cell Prolif 43:41–48

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Miwa S, Yano S, Zhang Y, Matsumoto Y, Uehara F, Yamamoto M, Hiroshima Y, Kimura H, Hayashi K, Yamamoto N, Bouvet M, Tsuchiya H, Hoffman RM, Zhao M (2012) Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice. Oncotarget 5:7119–7125

    Google Scholar 

  29. Miwa S, Yano S, Zhang Y, Matsumoto Y, Uehara F, Yamamoto M et al (2014) Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice. Oncotarget 5(16):7119–7125

    PubMed Central  PubMed  Google Scholar 

  30. Momiyama M, Zhao M, Kimura H, Tran B, Chishima T, Bouvet M, Endo I, Hoffman RM (2012) Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model. Cell Cycle 11:628–632

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Alpaugh ML, Tomlinson JS, Ye Y, Barsky SH (2002) Relationship of sialyl-Lewisx/a underexpression and E-cadherin overexpression in the lymphovascular embolus of inflammatory breast carcinoma. Am J Pathol 161:619–628

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Basso DM, Beattie MS, Bresnahan JC, Anderson DK, Faden AI, Gruner JA et al (1996) MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter animal spinal cord injury study. J Neurotrauma 13:343–359

    Article  CAS  PubMed  Google Scholar 

  33. Zhao M, Suetsugu A, Ma H, Zhang L, Liu F, Zhang Y et al (2012) Efficacy against lung metastasis with a tumor-targeting mutant of Salmonella typhimurium in immunocompetent mice. Cell Cycle 11:187–193

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Momiyama M, Suetsugu A, Chishima T, Bouvet M, Endo I, Hoffman RM (2013) Subcellular real-time imaging of the efficacy of temozolomide on cancer cells in the brain of live mice. Anticancer Res 33:103–106

    CAS  PubMed  Google Scholar 

  35. Momiyama M, Suetsugu A, Kimura H, Chishima T, Bouvet M, Endo I et al (2013) Dynamic subcellular imaging of cancer cell mitosis in the brain of live mice. Anticancer Res 33:1367–1371

    PubMed  Google Scholar 

  36. Momiyama M, Zhao M, Kimura H, Tran B, Chishima T, Bouvet M et al (2012) Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model. Cell Cycle 11:628–632

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Zhang Y, Tome Y, Suetsugu A, Zhang L, Zhang N, Hoffman RM et al (2012) Determination of the optimal route of administration of Salmonella typhimurium A1-R to target breast cancer in nude mice. Anticancer Res 32:2501–2508

    PubMed  Google Scholar 

  38. Tome Y, Zhang Y, Momiyama M, Maehara H, Kanaya F, Tomita K et al (2013) Primer dosing of S. typhimurium A1-R potentiates tumor-targeting and efficacy in immunocompetent mice. Anticancer Res 33:97–102

    PubMed  Google Scholar 

  39. Furukawa T, Kubota T, Watanabe M, Kitajima M, Hoffman RM (1993) A novel “patient-like” treatment model of human pancreatic cancer constructed using orthotopic transplantation of histologically intact human tumor tissue in nude mice. Cancer Res 53:3070–3072

    CAS  PubMed  Google Scholar 

  40. Fu X, Guadagni F, Hoffman RM (1992) A metastatic nude mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens. Proc Natl Acad Sci U S A 89:5645–5649

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Hoffman RM (1999) Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Invest New Drugs 17:343–359

    Article  CAS  PubMed  Google Scholar 

  42. Bouvet M, Wang J-W, Nardin SR, Nassirpour R, Yang M, Baranov E et al (2002) Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model. Cancer Res 62:1534–1540

    CAS  PubMed  Google Scholar 

  43. Bouvet M, Yang M, Nardin S, Wang X, Jiang P, Baranov E et al (2000) Chronologically-specific metastatic targeting of human pancreatic tumors in orthotopic models. Clin Exp Metastasis 18:213–218

    Article  CAS  PubMed  Google Scholar 

  44. Yamauchi K, Yang M, Jiang P, Xu M, Yamamoto N, Tsuchiya H et al (2006) Development of real-time subcellular dynamic multicolor imaging of cancer-cell trafficking in live mice with a variable-magnification whole-mouse imaging system. Cancer Res 66:4208–4214

    Article  CAS  PubMed  Google Scholar 

  45. Kim MP, Evans DB, Wang H, Abbruzzese JL, Fleming JB, Gallick GE (2009) Generation of orthotopic and heterotopic human pancreatic cancer xenografts in immunodeficient mice. Nat Protoc 4:1670–1680

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Kim MP, Truty MJ, Choi W, Kang Y, Chopin-Lally X, Gallick GE et al (2012) Molecular profiling of direct xenograft tumors established from human pancreatic adenocarcinoma after neoadjuvant therapy. Ann Surg Oncol 19(Suppl3):S395–S403

    Article  PubMed Central  PubMed  Google Scholar 

  47. Yang M, Reynoso J, Bouvet M, Hoffman RM (2009) A transgenic red fluorescent protein-expressing nude mouse for color-coded imaging of the tumor microenvironment. J Cell Biochem 106:279–284

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Katz M, Takimoto S, Spivack D, Moossa AR, Hoffman RM, Bouvet M (2003) A novel red fluorescent protein orthotopic pancreatic cancer model for the preclinical evaluation of chemotherapeutics. J Surg Res 113:151–160

    Article  CAS  PubMed  Google Scholar 

  49. Yang M, Jiang P, Hoffman RM (2007) Whole-body subcellular multicolor imaging of tumor-host interaction and drug response in real time. Cancer Res 67:5195–5200

    Article  CAS  PubMed  Google Scholar 

  50. Hassanein MK, Suetsugu A, Saji S, Moriwaki H, Bouvet M, Moossa AR et al (2011) Stem-like and non-stem human pancreatic cancer cells distinguished by morphology and metastatic behavior. J Cell Biochem 112:3549–3554

    Article  CAS  PubMed  Google Scholar 

  51. Zhang Y, Zhang N, Su S, Hoffman RM, Zhao M (2013) Salmonella typhimurium A1-R tumor targeting in immunocompetent mice is enhanced by a traditional Chinese medicine herbal mixture. Anticancer Res 33:1837–1843

    PubMed  Google Scholar 

  52. Yano S, Zhang Y, Zhao M, Hiroshima Y, Miwa S, Uehara F et al (2014) Tumor-targeting Salmonella typhimurium A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy. Cell Cycle 13(24):3958–3963

    Article  CAS  PubMed  Google Scholar 

  53. Hoffman RM, Zhao M (2006) Whole-body imaging of bacterial infection and antibiotic response. Nat Protoc 1:2988–2994

    Article  CAS  PubMed  Google Scholar 

  54. Yang M, Luiken G, Baranov E, Hoffman RM (2005) Facile whole-body imaging of internal fluorescent tumors in mice with an LED flashlight. Biotechniques 39:170–172

    Article  CAS  PubMed  Google Scholar 

  55. Yamauchi K, Yang M, Jiang P, Xu M, Yamamoto N, Tsuchiya H, Tomita K, Moossa AR, Bouvet M, Hoffman RM (2006) Development of real-time subcellular dynamic multicolor imaging of cancer cell-trafficking in live mice with a variable-magnification whole-mouse imaging system. Cancer Res 66:4208–4212

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, 92111, USA

    Robert M. Hoffman Ph.D.

  2. Department of Surgery, University of California San Diego, 200 West Arbor Drive, San Diego, CA, 92103-8220, USA

    Robert M. Hoffman Ph.D.

Authors
  1. Robert M. Hoffman Ph.D.
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Correspondence to Robert M. Hoffman Ph.D. .

Editor information

Editors and Affiliations

  1. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Wolfgang Walther

  2. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Berlin, Germany

    Ulrike Stein

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Hoffman, R.M. (2015). Back to the Future: Are Tumor-Targeting Bacteria the Next-Generation Cancer Therapy?. In: Walther, W., Stein, U. (eds) Gene Therapy of Solid Cancers. Methods in Molecular Biology, vol 1317. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2727-2_14

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  • DOI: https://doi.org/10.1007/978-1-4939-2727-2_14

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2726-5

  • Online ISBN: 978-1-4939-2727-2

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