Salmonella and cancer: from pathogens to therapeutics

• Autorzy: Chorobik P. , Czaplicki D. , Ossysek K. , Bereta J.
• Języki publikacji: EN

Abstrakty

EN

 Bacterial cancer therapy is a concept more than 100 years old - yet, all things considered, it is still in early development. While the use of many passive therapeutics is hindered by the complexity of tumor biology, bacteria offer unique features that can overcome these limitations. Microbial metabolism, motility and sensitivity can lead to site-specific treatment, highly focused on the tumor and safe to other tissues. Activation of tumor-specific immunity is another important mechanism of such therapies. Several bacterial strains have been evaluated as cancer therapeutics so far, Salmonella Typhimurium being one of the most promising. S. Typhimurium and its derivatives have been used both as direct tumoricidal agents and as cancer vaccine vectors. VNP20009, an attenuated mutant of S. Typhimurium, shows significant native toxicity against murine tumors and was studied in a first-in-man phase I clinical trial for toxicity and anticancer activity. While proved to be safe in cancer patients, insufficient tumor colonization of VNP20009 was identified as a major limitation for further clinical development. Antibody-fragment-based targeting of cancer cells is one of the few approaches proposed to overcome this drawback.

Słowa kluczowe

EN

Salmonella; cancer; pathogen; therapeutics; bacterial therapy; immunotherapy; cancer vaccine; tumour targeting

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2013
• Tom: 60
• Numer: 3
• Opis fizyczny: p.285-297,fig.,ref.

Twórcy

autor

Chorobik P.

• Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Krakow, Poland

autor

Czaplicki D.

• Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Krakow, Poland

autor

Ossysek K.

• Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Krakow, Poland

autor

Bereta J.

• Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Krakow, Poland

Bibliografia

• Ahmad S, Casey G, Cronin M, Rajendran S, Sweeney P, Tangney M, O'Sullivan GC (2011) Induction of effective antitumor response after mucosal bacterial vector mediated DNA vaccination with endogenous prostate cancer specific antigen. J Urol 186: 687-693. 
• Alexandroff AB, Jackson AM, O'Donnell MA, James K (1999) BCG immunotherapy of bladder cancer: 20 years on. Lancet 353: 1689-1694. 
• Altieri DC (2003) Validating survivin as a cancer therapeutic target. Nat Rev Cancer 3: 46-54 
• Anderson DG, Kowalczykowski SC (1998) Reconstitution of an SOS response pathway: derepression of transcription in response to DNA breaks. Cell 95: 975-979. 
• Angelakopoulos H, Hohmann EL (2000) Pilot study of phoP/phoQ-deleted Salmonella enterica serovar typhimurium expressing Helicobacter pylori urease in adult volunteers. Infect Immun 68: 2135-2141. 
• Avogadri F, Martinoli C, Petrovska L, Chiodoni C, Transidico P, Bronte V, Longhi R, Colombo MP, Dougan G, Rescigno M (2005) Cancer immunotherapy based on killing of Salmonella-infected tumor cells. Cancer Res 65: 3920-3927. 
• Bajaj V, Hwang C, Lee CA (1995) hilA is a novel ompR/toxR family member that activates the expression of Salmonella typhimurium invasion genes. Mol Microbiol 18: 715-727. 
• Baumler AJ, Tsolis RM, Ficht TA, Adams LG (1998) Evolution of host adaptation in Salmonella enterica. Infect Immun 66: 4579-4587. 
• Bereta M, Hayhurst A, Gajda M, Chorobik P, Targosz M, Marcinkiewicz J, Kaufman HL (2007) Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies. Vaccine 25: 4183-4192. 
• Bermudes D, Zheng LM, King IC (2002) Live bacteria as anticancer agents and tumor-selective protein delivery vectors. Curr Opin Drug Discov Devel 5: 194-199. 
• Blache CA, Manuel ER, Kaltcheva TI, Wong AN, Ellenhorn JD, Blazar BR, Diamond DJ (2012) Systemic delivery of Salmonella typhimurium transformed with IDO shRNA enhances intratumoral vector colonization and suppresses tumor growth. Cancer Res 72: 6447-6456. 
• Cao HD, Yang YX, Lu L, Liu SN, Wang PL, Tao XH, Wang LJ, Xiang TX (2010) Attenuated Salmonella typhimurium carrying TRAIL and VP3 genes inhibits the growth of gastric cancer cells in vitro and in vivo. Tumori 96: 296-303. 
• Chakravortty D, Hansen-Wester I, Hensel M (2002) Salmonella pathogenicity island 2 mediates protection of intracellular Salmonella from reactive nitrogen intermediates. J Exp Med 195: 1155-1166. 
• Chatfield SN, Charles IG, Makoff AJ, Oxer MD, Dougan G, Pickard D, Slater D, Fairweather NF (1992) Use of the nirB promoter to direct the stable expression of heterologous antigens in Salmonella oral vaccine strains: development of a single-dose oral tetanus vaccine. Biotechnology (NY) 10: 888-892. 
• Chen J, Yang B, Cheng X, Qiao Y, Tang B, Chen G, Wei J, Liu X, Cheng W, Du P, Huang X, Jiang W, Hu Q, Hu Y, Li J, Hua ZC (2012) Salmonella-mediated tumor-targeting TRAIL gene therapy significantly suppresses melanoma growth in mouse model. Cancer Sci 103: 325-333. 
• Chorobik P, Marcinkiewicz M (2011) Therapeutic vaccines based on genetically modified Salmonella: a novel strategy in cancer immunotherapy. Polskie Archiwum Medycyny Wewnętrznej 121: 461-466. 
• Chou CK, Hung JY, Liu JC, Chen CT, Hung MC (2006) An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular carcinoma and colon cancer that express alpha-fetoprotein. Cancer Gene Ther 13: 746-752. 
• Dai MS, Nitcheu-Tefit J, Alcock S, Ramirez-Jimenez F, Chao TY, Baril P, Rocha M, Brett SJ, Stauss HJ, Vassaux G (2009) Development of an Escherichia coli expressing listeriolysin-O vaccine against Wilms tumor gene 1-expressing tumors. J Immunother 32: 845-855. 
• Dang LH, Bettegowda C, Huso DL, Kinzler KW, Vogelstein B (2001) Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci USA 98: 15155-15160. 
• Deng Y, Lin Y, Wu X (2002) TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO. Genes Dev 16: 33-45. 
• Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA (2012) Invasive non-typhoidal Salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 379: 2489-2499. 
• Fest S, Huebener N, Bleeke M, Durmus T, Stermann A, Woehler A, Baykan B, Zenclussen AC, Michalsky E, Jaeger IS, Preissner R, Hohn O, Weixler S, Gaedicke G, Lode HN (2009) Survivin minigene DNA vaccination is effective against neuroblastoma. Int J Cancer 125: 104-114. 
• Forbes NS (2010) Engineering the perfect (bacterial) cancer therapy. Nat Rev Cancer 10: 785-794. 
• 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. 
• Fulda S, Wick W, Weller M, Debatin KM (2002) Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med 8: 808-815. 
• Galan JE, Collmer A (1999) Type III secretion machines: bacterial devices for protein delivery into host cells. Science 284: 1322-1328. 
• Galmbacher K, Heisig M, Hotz C, Wischhusen J, Galmiche A, Bergmann B, Gentschev I, Goebel W, Rapp UR, Fensterle J (2010) Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression. PLoS One 5: e9572. 
• Ganai S, Arenas RB, Forbes NS (2009) Tumour-targeted delivery of TRAIL using Salmonella typhimurium enhances breast cancer survival in mice. Br J Cancer 101: 1683-1691. 
• Garmory HS, Brown KA, Titball RW (2002) Salmonella vaccines for use in humans: present and future perspectives. FEMS Microbiol Rev 26: 339-353. 
• Green PN, Hoption Cann SA (2007) Bacterial anti-cancer vaccines: a science frozen in time. Microbiologist 8: 29-34.
• Guibourdenche M, Roggentin P, Mikoleit M, Fields PI, Bockemuhl J, Grimont PA, Weill FX (2010) Supplement 2003-2007 (No. 47) to the White-Kauffmann-Le Minor scheme. Res Microbiol 161: 26-29. 
• Guo CC, Ding J, Pan BR, Yu ZC, Han QL, Meng FP, Liu N, Fan DM (2003) Development of an oral DNA vaccine against MG7-Ag of gastric cancer using attenuated Salmonella typhimurium as carrier. World J Gastroenterol 9: 1191-1195. 
• Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Hoffman RM (2009a) Cancer metastasis directly eradicated by targeted therapy with a modified Salmonella typhimurium. J Cell Biochem 106: 992-998. 
• Hayashi K, Zhao M, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Kishimoto H, Bouvet M, Hoffman RM (2009b) 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. 
• Heimann DM, Rosenberg SA (2003) Continuous intravenous administration of live genetically modified Salmonella typhimurium in patients with metastatic melanoma. J Immunother 26: 179-180. 
• Hoiseth SK, Stocker BA (1985) Genes aroA and serC of Salmonella typhimurium constitute an operon. J Bacteriol 163: 355-361. 
• Hong EH, Chang SY, Lee BR, Pyun AR, Kim JW, Kweon MN, Ko HJ (2013) Intratumoral injection of attenuated Salmonella vaccine can induce tumor microenvironmental shift from immune suppressive to immunogenic. Vaccine 31: 1377-1384. 
• Huebener N, Fest S, Strandsby A, Michalsky E, Preissner R, Zeng Y, Gaedicke G, Lode HN (2008) A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity. Mol Cancer Ther 7: 2241-2251. 
• Hylander BL, Pitoniak R, Penetrante RB, Gibbs JF, Oktay D, Cheng J, Repasky EA (2005) The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice. J Transl Med 3: 22. 
• Janssen R, van der Straaten T, van Diepen A, van Dissel JT (2003) Responses to reactive oxygen intermediates and virulence of Salmonella typhimurium. Microbes Infect 5: 527-534. 
• Jarosz M, Jazowiecka-Rakus J, Cichon T, Glowala-Kosinska M, Smolarczyk R, Smagur A, Malina S, Sochanik A, Szala S (2013) Therapeutic antitumor potential of endoglin-based DNA vaccine combined with immunomodulatory agents. Gene Ther 20: 262-273. 
• Jellbauer S, Panthel K, Hetrodt JH, Russmann H (2012) CD8 T-cell induction against vascular endothelial growth factor receptor 2 by Salmonella for vaccination purposes against a murine melanoma. PLoS One 7: e34214. 
• Jepson MA, Clark MA (2001) The role of M cells in Salmonella infection Microbes Infect 3: 1183-1190. 
• Jesenberger V, Procyk KJ, Yuan J, Reipert S, Baccarini M (2000) Salmonella-induced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis. J Exp Med 192: 1035-1046. 
• Karbach J, Neumann A, Brand K, Wahle C, Siegel E, Maeurer M, Ritter E, Tsuji T, Gnjatic S, Old LJ, Ritter G, Jager E (2012) Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity. Clin Cancer Res 18: 5449-5459. 
• Kawai K, Miyazaki J, Joraku A, Nishiyama H, Akaza H (2013) Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: current understanding and perspectives on engineered BCG vaccine. Cancer Sci 104: 22-27. 
• Kim JM, Eckmann L, Savidge TC, Lowe DC, Witthoft T, Kagnoff MF (1998) Apoptosis of human intestinal epithelial cells after bacterial invasion. J Clin Invest 102: 1815-1823. 
• 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. 
• Knodler LA, Vallance BA, Celli J, Winfree S, Hansen B, Montero M, Steele-Mortimer O (2010) Dissemination of invasive Salmonella via bacterial-induced extrusion of mucosal epithelia. Proc Natl Acad Sci USA 107: 17733-17738. 
• Kolyva S, Waxin H, Popoff MY (1992) The Vi antigen of Salmonella typhi: molecular analysis of the viaB locus. J Gen Microbiol 138: 297-304. 
• LeBlanc HN, Ashkenazi A (2003) Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 10: 66-75. 
• Lee KC, Zheng L-M, Luo X, Clairmont C, Fischer J, Margitich D, Turnier J, Almassian B, Bermudes D, King I (2000) Comparative evaluation of the acute toxic effects in monkeys, pigs and mice of a genetically engineered Salmonella strain (VNP20009) being developed as an antitumor agent. Int J Toxicol 19: 19-25.
• Loeffler M, Le'Negrate G, Krajewska M, Reed JC (2008) IL-18-producing Salmonella inhibit tumor growth. Cancer Gene Ther 15: 787-794. 
• Loeffler M, Le'Negrate G, Krajewska M, Reed JC (2009) Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth. Cancer Immunol Immunother 58: 769-775. 
• Low KB, Ittensohn M, Luo X, Zheng LM, King I, Pawelek JM, Bermudes D (2004) Construction of VNP20009: a novel, genetically stable antibiotic-sensitive strain of tumor-targeting Salmonella for parenteral administration in humans. Methods Mol Med 90: 47-60. 
• Lucas RL, Lostroh CP, DiRusso CC, Spector MP, Wanner BL, Lee CA (2000) Multiple factors independently regulate hilA and invasion gene expression in Salmonella enterica serovar typhimurium. J Bacteriol 182: 1872-1882. 
• Malik-Kale P, Jolly CE, Lathrop S, Winfree S, Luterbach C, Steele-Mortimer O (2011) Salmonella - at home in the host cell. Front Microbiol 2: 125. 
• Malik-Kale P, Winfree S, Steele-Mortimer O (2012) The bimodal lifestyle of intracellular Salmonella in epithelial cells: replication in the cytosol obscures defects in vacuolar replication. PLoS One 7: e38732. 
• Manuel ER, Blache CA, Paquette R, Kaltcheva TI, Ishizaki H, Ellenhorn JD, Hensel M, Metelitsa L, Diamond DJ (2011) Enhancement of cancer vaccine therapy by systemic delivery of a tumor-targeting Salmonella-based STAT3 shRNA suppresses the growth of established melanoma tumors. Cancer Res 71: 4183-4191. 
• Martinez-Argudo I, Jepson MA (2008) Salmonella translocates across an in vitro M cell model independently of SPI-1 and SPI-2. Microbiology 154: 3887-3894. 
• McCarthy EF (2006) The toxins of William B Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J 26: 154-148. 
• McClelland M, Sanderson KE, Spieth J, Clifton SW, Latreille P, Courtney L, Porwollik S, Ali J, Dante M, Du F, Hou S, Layman D, Leonard S, Nguyen C, Scott K, Holmes A, Grewal N, Mulvaney E, Ryan E, Sun H, Florea L, Miller W, Stoneking T, Nhan M, Waterston R, Wilson RK (2001) Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413: 852-856. 
• Meng FP, Ding J, Yu ZC, Han QL, Guo CC, Liu N, Fan DM (2005) Oral attenuated Salmonella typhimurium vaccine against MG7-Ag mimotope of gastric cancer. World J Gastroenterol 11: 1833-1836. 
• Meng JZ, Dong YJ, Huang H, Li S, Zhong Y, Liu SL, Wang YD (2010) Oral vaccination with attenuated Salmonella enterica strains encoding T-cell epitopes from tumor antigen NY-ESO-1 induces specific cytotoxic T-lymphocyte responses. Clin Vaccine Immunol 17: 889-894. 
• Monack DM, Raupach B, Hromockyj AE, Falkow S (1996) Salmonella typhimurium invasion induces apoptosis in infected macrophages. Proc Natl Acad Sci USA 93: 9833-9838. 
• 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. 
• Niethammer AG, Lubenau H, Mikus G, Knebel P, Hohmann N, Leowardi C, Beckhove P, Akhisaroglu M, Ge Y, Springer M, Grenacher L, Buchler MW, Koch M, Weitz J, Haefeli WE, Schmitz-Winnenthal FH (2012) Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer. BMC Cancer 12: 361. 
• Nishikawa H, Sato E, Briones G, Chen LM, Matsuo M, Nagata Y, Ritter G, Jager E, Nomura H, Kondo S, Tawara I, Kato T, Shiku H, Old LJ, Galan JE, Gnjatic S (2006) In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines. J Clin Invest 116: 1946-1954. 
• Paglia P, Medina E, Arioli I, Guzman CA, Colombo MP (1998) Gene transfer in dendritic cells, induced by oral DNA vaccination with Salmonella typhimurium, results in protective immunity against a murine fibrosarcoma. Blood 92: 3172-3176. 
• Panthel K, Meinel KM, Domenech VE, Retzbach H, Igwe EI, Hardt WD, Russmann H (2005) Salmonella pathogenicity island 2-mediated overexpression of chimeric SspH2 proteins for simultaneous induction of antigen-specific CD4 and CD8 T cells. Infect Immun 73: 334-341. 
• Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ (2002) Typhoid fever. N Engl J Med 347: 1770-1782. 
• Paterson Y, Guirnalda PD, Wood LM (2010) Listeria and Salmonella bacterial vectors of tumor-associated antigens for cancer immunotherapy. Semin Immunol 22: 183-189. 
• Pawelek JM, Low KB, Bermudes D (1997) Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res 57: 4537-4544. 
• Pei Z, Chu L, Zou W, Zhang Z, Qiu S, Qi R, Gu J, Qian C, Liu X (2004) An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice. Hepatology 39: 1371-1381. 
• Raupach B, Kaufmann S H (2001) Bacterial virulence, proinflammatory cytokines and host immunity: how to choose the appropriate Salmonella vaccine strain? Microbes Infect 3: 1261-1269. 
• Raupach B, Kurth N, Pfeffer K, Kaufmann SH (2003) Salmonella typhimurium strains carrying independent mutations display similar virulence phenotypes yet are controlled by distinct host defense mechanisms. J Immunol 170: 6133-6140. 
• Richardson MA, Ramirez T, Russell NC, Moye LA (1999) Coley toxins immunotherapy: a retrospective review. Altern Ther Health Med 5: 42-47. 
• Saltzman DA, Heise CP, Hasz DE, Zebede M, Kelly SM, Curtiss R 3rd, 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. 
• Saunders NA, Simpson F, Thompson EW, Hill MM, Endo-Munoz L, Leggatt G, Minchin RF, Guminski A (2012) Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives. EMBO Mol Med 4: 675-684. 
• Schroeder N, Mota LJ, Meresse S (2011) Salmonella-induced tubular networks. Trends Microbiol 19: 268-277. 
• Shanker A, Brooks AD, Tristan CA, Wine JW, Elliott PJ, Yagita H, Takeda K, Smyth MJ, Murphy WJ, Sayers TJ (2008) Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. J Natl Cancer Inst 100: 649-662. 
• Shwartzman G (1928) Studies on Bacillus typhosus toxic substances: i phenomenon of local skin reactivity to B typhosus culture filtrate. J Exp Med 48: 247-68. 
• Shwartzman G (1935) Hemorrhagic necrosis and regression sarcoma 180. Science 82: 201. 
• Singh R, Wallecha A (2011) Cancer immunotherapy using recombinant Listeria monocytogenes: transition from bench to clinic. Hum Vaccin 7: 497-505. 
• Song J, Willinger T, Rongvaux A, Eynon EE, Stevens S, Manz MG, Flavell RA, Galan JE (2010) A mouse model for the human pathogen Salmonella typhi. Cell Host Microbe 8: 369-376. 
• St Jean AT, Zhang M, Forbes NS (2008) Bacterial therapies: completing the cancer treatment toolbox. Curr Opin Biotechnol 19: 511-517. 
• Steele-Mortimer O (2008) The Salmonella-containing vacuole: moving with the times. Curr Opin Microbiol 11: 38-45. 
• Steele-Mortimer O, Meresse S, Gorvel JP, Toh BH, Finlay BB (1999) Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway. Cell Microbiol 1: 33-49. 
• Stritzker J, Weibel S, Seubert C, Gotz A, Tresch A, van Rooijen N, Oelschlaeger TA, Hill PJ, Gentschev I, Szalay AA (2010) Enterobacterial tumor colonization in mice depends on bacterial metabolism and macrophages but is independent of chemotaxis and motility. Int J Med Microbiol 300: 449-56. 
• Strugnell R, Dougan G, Chatfield S, Charles I, Fairweather N, Tite J, Li JL, Beesley J, Roberts M (1992) Characterization of a Salmonella typhimurium aro vaccine strain expressing the P 69 antigen of Bordetella pertussis. Infect Immun 60: 3994-4002. 
• Swart AL, Hensel M (2012) Interactions of Salmonella enterica with dendritic cells. Virulence 3 (Epub ahead of print). 
• Tangney M, van Pijkeren JP, Gahan CG (2010) The use of Listeria monocytogenes as a DNA delivery vector for cancer gene therapy. Bioeng Bugs 1: 284-287. 
• Thamm DH, Kurzman ID, King I, Li Z, Sznol M, Dubielzig RR, Vail DM, MacEwen EG (2005) Systemic administration of an attenuated, tumor-targeting Salmonella typhimurium to dogs with spontaneous neoplasia: phase I evaluation. Clin Cancer Res 11: 4827-4834. 
• Tindall BJ, Grimont PA, Garrity GM, Euzeby JP (2005) Nomenclature and taxonomy of the genus Salmonella. Int J Syst Evol Microbiol 55: 521-524. 
• Toley BJ, Forbes NS (2012) Motility is critical for effective distribution and accumulation of bacteria in tumor tissue. Integr Biol (Camb) 4: 165-176. 
• Tome Y, Zhang Y, Momiyama M, Maehara H, Kanaya F, Tomita K, Tsuchiya H, Bouvet M, Hoffman RM, Zhao M (2013) Primer dosing of S. typhimurium A1-R potentiates tumor-targeting and efficacy in immunocompetent mice. Anticancer Res 33: 97-102. 
• Toso JF, Gill VJ, Hwu P, Marincola FM, Restifo NP, Schwartzentruber DJ, Sherry RM, Topalian SL, Yang JC, Stock F, Freezer LJ, Morton KE, Seipp C, Haworth L, Mavroukakis S, White D, MacDonald S, Mao J, Sznol M, Rosenberg SA (2002) Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J Clin Oncol 20: 142-152. 
• Tran J, Rak J, Sheehan C, Saibil SD, LaCasse E, Korneluk RG, Kerbel RS (1999) Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. Biochem Biophys Res Commun 264: 781-788. 
• Umer B, Good D, Anne J, Duan W, Wei MQ (2012) Clostridial spores for cancer therapy: targeting solid tumour microenvironment. J Toxicol 2012: 862764. 
• Velge P, Wiedemann A, Rosselin M, Abed N, Boumart Z, Chausse AM, Grepinet O, Namdari F, Roche SM, Rossignol A, Virlogeux-Payant I (2012) Multiplicity of Salmonella entry mechanisms, a new paradigm for Salmonella pathogenesis. Microbiologyopen 1: 243-258. 
• Vendrell A, Gravisaco MJ, Pasetti MF, Croci M, Colombo L, Rodriguez C, Mongini C, Waldner CI (2011) A novel Salmonella Typhi-based immunotherapy promotes tumor killing via an antitumor Th1-type cellular immune response and neutrophil activation in a mouse model of breast cancer. Vaccine 29: 728-736. 
• Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5: 157-163. 
• Xiang R, Primus FJ, Ruehlmann JM, Niethammer AG, Silletti S, Lode HN, Dolman CS, Gillies SD, Reisfeld RA (2001) A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice. J Immunol 167: 4560-4565. 
• Xiong G, Husseiny MI, Song L, Erdreich-Epstein A, Shackleford GM, Seeger RC, Jackel D, Hensel M, Metelitsa LS (2010) Novel cancer vaccine based on genes of Salmonella pathogenicity island 2. Int J Cancer 126: 2622-2634. 
• Yagita H, Takeda K, Hayakawa Y, Smyth MJ, Okumura K (2004) TRAIL and its receptors as targets for cancer therapy. Cancer Sci 95: 777-783. 
• Yoon WS, Chae YS, Hong J, Park YK (2011) Antitumor therapeutic effects of a genetically engineered Salmonella typhimurium harboring TNF-alpha in mice. Appl Microbiol Biotechnol 89: 1807-1819. 
• Yrlid U, Wick MJ (2000) Salmonella-induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells. J Exp Med 191: 613-624. 
• Yu B, Yang M, Shi L, Yao Y, Jiang Q, Li X, Tang LH, Zheng B J, Yuen KY, Smith DK, Song E, Huang JD (2012) Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain. Sci Rep 2: 436. 
• Zhang XD, Zhang XY, Gray CP, Nguyen T, Hersey P (2001) Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of human melanoma is regulated by smac/DIABLO release from mitochondria. Cancer Res 61: 7339-7348. 
• Zhang Y, Tome Y, Suetsugu A, Zhang L, Zhang N, Hoffman RM, Zhao M (2012a) Determination of the optimal route of administration of Salmonella typhimurium A1-R to target breast cancer in nude mice. Anticancer Res 32: 2501-2508. 
• Zhang Y, Xia L, Zhang X, Ding X, Yan F, Wu F (2012b) Escherichia coli Nissle 1917 targets and restrains mouse B16 melanoma and 4T1 breast tumors through expression of azurin protein. Appl Environ Microbiol 78: 7603-7610. 
• 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 USA 104: 10170-10174. 
• 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 USA 102: 755-760. 
• 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. 
• Zhu X, Zhou P, Cai J, Yang G, Liang S, Ren D (2010) Tumor antigen delivered by Salmonella III secretion protein fused with heat shock protein 70 induces protection and eradication against murine melanoma. Cancer Sci 101: 2621-2628. 
• Zhuang SM, Shvarts A, van Ormondt H, Jochemsen AG, van der Eb AJ, Noteborn MH (1995) Apoptin, a protein derived from chicken anemia virus, induces p53-independent apoptosis in human osteosarcoma cells. Cancer Res 55: 486-489.