Prophylactic anti-tumor immunity against a murine fibrosarcoma triggered by the Salmonella type III secretion system

Panthel, Klaus; Meinel, Katrin M.; Domènech, Victòria E. Sevil; Geginat, Gernot; Linkemann, Kathrin; Busch, Dirk H.; Rüssmann, Holger

doi:10.1016/j.micinf.2006.07.004

Cited by 38 publications

(36 citation statements)

References 28 publications

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“…The resulting products were then hybridized to an array of 387,000 oligonucleotide sequences positioned at 12-base intervals around the Typhimurium genome (using the manufacturer's protocol). 6 Spot intensities were normalized based on total signal in each channel. The enrichment of genomic regions was measured by the intensity ratio of the tumor or the spleen sample versus the input library (library-0).…”

Section: Resultsmentioning

confidence: 99%

“…Salmonella enterica serovar typhimurium is a facultative anaerobic bacterium that naturally accumulates in a wide variety of solid tumors as opposed to normal tissue (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Avirulent mutants of this bacterium prefer tumors over normal tissue at ratios that range between 250:1 and 9,000:1 (1,11), and can lead to tumor reduction or cures in animal models (2).…”

Section: Introductionmentioning

confidence: 99%

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Salmonella Promoters Preferentially Activated Inside Tumors

et al. 2008

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Salmonella enterica and avirulent derivatives prefer solid tumors over normal tissue in animal models. The identification of endogenous Salmonella promoters that are preferentially activated in tumors could further our understanding of this phenomenon. Toward this goal, a random library of S. enterica typhimurium 14028 genomic DNA was cloned upstream of a promoterless gene encoding the green fluorescent protein (GFP) TurboGFP. A population of Salmonella containing this library was injected i.v. into tumor-free nude mice and into human PC3 prostate tumors growing subcutaneously in nude mice. After 2 days, fluorescence-activated cell sorting was used to enrich for bacterial clones expressing GFP from spleens or tumors. The resulting libraries were hybridized to an oligonucleotide tiling array of the Salmonella genome. Eighty-six intergenic regions were found to be enriched in tumor samples but not in spleen. Twenty of these candidate promoters were also detected in the sequences of 100 random clones from a library enriched for expression in bacteria growing in tumors. Three candidate promoter clones were individually tested in vivo, and enhanced GFP expression in bacteria growing in tumor relative to spleen was confirmed. Two of the three clones (pflE and ansB promoter regions) are known to be induced in hypoxic conditions that pertain to many tumors. For many of the other candidate promoters preferentially induced in bacteria growing in tumors, regulatory mechanisms may not be related to hypoxia. The expression of therapeutics in Salmonella under the regulation of one or more promoters that are activated preferentially in tumors has the potential to improve the targeting of drug delivery. [Cancer Res 2008;68(12):4827–32]

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Salmonella Promoters Preferentially Activated Inside Tumors

et al. 2008

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“…Oridonin has been shown to possess cell cycle arrest, apoptosis and autophagy-inducing activities towards a variety of cancer cells (14). Besides, oridonin is able to trigger ROS generation and perturb redox balance in hepatocellular carcinoma cells (15 (16,17).…”

Section: Introductionmentioning

confidence: 99%

Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells

Hua¹

2011

Int J Oncol

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Abstract. Although arsenic trioxide (As 2 O 3 ) has been successfully employed in treatment of patients with APL (acute promyelocytic leukemia), the sensitivity of solid tumor cells to this treatment was much lower than APL cells. The single agent of As 2 O 3 was inefficient for treatment of hepatocellular carcinoma (HCC) in phase II trial demonstrating that new modalities of treatment with enhanced therapeutic effect are needed. In this study, we showed that oridonin, a diterpenoid isolated from traditional Chinese medicine Rabdosia rubescences, greatly potentiated apoptosis induced by As 2 O 3 in hepatocellular carcinoma cells. The synergistic pro-apoptosis effect of combination of these two drugs led to increase in intracellular reactive oxygen species (ROS) level and N-acetyl-L-cysteine (NAC), a thiolcontaining anti-oxidant, was able to completely block the effect. The combination treatment induced ROS-dependent decrease in mitochondrial membrane potential (MMP) decrease, and relocation of Bax and cytochrome C. Besides, oridonin dramatically increased the intracellular Ca 2+ overload triggered by As 2 O 3 . Furthermore, the co-treatment of oridonin and As 2 O 3 induced ROS-mediated down-regulation of Akt and XIAP, and inhibition of NF-κB activation. The two drug combination enhanced tumor suppression activity in murine HCC model compared with single agent treatment in vivo. These findings demonstrate that oridonin can sensitize hepatocellular carcinoma cells to As 2 O 3 treatment and will facilitate the optimization of As 2 O 3 therapy for HCC patients.

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“…This approach has proved efficient for priming antigen-specific CD8 þ T cells against tumor antigens. 44,45 All of these data demonstrated that if the heterologous antigen was delivered via the Salmonella carrier in a secreted form, it was able to induce CD8 response.…”

Section: Discussionmentioning

confidence: 92%

Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B

et al. 2007

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Prostate cancer is the most common malignant tumor in men and is normally associated with increased serum levels of prostatespecific antigen (PSA). Therefore, PSA is one potential target for a prostate cancer vaccine. In this study we analyzed the functionality of new bacterial PSA vaccines, expressed and secreted via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of Type I secretion systems (T1SS) using an attenuated Salmonella enterica serovar Typhimurium aroA strain as carrier. The data demonstrate that a bacterial live vaccine encompassing T1SS in combination with cholera toxin subunit B can be successfully used for delivery of PSA to induce cytotoxic CD8 þ T-cell responses resulting in an efficient prevention of tumor growth in mice.

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Prophylactic anti-tumor immunity against a murine fibrosarcoma triggered by the Salmonella type III secretion system

Cited by 38 publications

References 28 publications

Salmonella Promoters Preferentially Activated Inside Tumors

Salmonella Promoters Preferentially Activated Inside Tumors

Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells

Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B

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