Salmonella SL7207 application is the most effective DNA vaccine delivery method for successful tumor eradication in a murine model for neuroblastoma

Berger, Elisa; Soldati, Rocío; Huebener, Nicole; Hohn, Oliver; Stermann, Alexander; Durmus, Tahir; Lobitz, Stephan; Zenclussen, Ana Claudia; Christiansen, Holger; Lode, Holger N.; Fest, Stefan

doi:10.1016/j.canlet.2012.12.026

Cited by 55 publications

(34 citation statements)

References 49 publications

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“…Immunization with attenuated Salmonella harboring plasmid DNA vaccines proved to be effective in DNA delivery and subsequent induction of immunity against the encoded antigens. A previous study found that DNA vaccines delivered by attenuated Salmonella SL7207 induced a stronger cellular antitumor immune response than gene gun approaches, or injection of lentivirally transduced bone marrow-derived DCs (19). Our study revealed that the tumor DNA vaccine delivered by Salmonella promoted the proliferation of CD8 þ T cells in vivo.…”

Section: Discussionmentioning

confidence: 53%

“…How the DNA vaccine is delivered to the host immune system is critical for induction of an effective antigen-specific immune response. DNA-encoding specific epitopes can be incorporated as a live vaccine delivered by attenuated, nonreplicating Salmonella typhimurium (SL7207), which transport the DNA vaccine through DCs and macrophages (19)(20)(21)(22). The attenuated bacteria are captured by antigen-presenting cells and die due to an internal mutation, liberating multiple copies of DNA, and activating CD8 þ T-cell responses presented by these APCs to stimulate CD4 þ T cells (25,26).…”

Section: Introductionmentioning

confidence: 99%

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Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Zhao

Liu

et al. 2017

Cancer Immunology Research

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Stimulation of tumor-specific responses in both CD4 þ and CD8 þ T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated Salmonella strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the Salmonella tumor vaccine. The vaccine activated tumor-specific CD4 þ and CD8 þ T-cell responses, with increased T-cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity. CD4 þ or CD8 þ T-cell depletion resulted in the loss of antitumor activity of the Salmonella tumor vaccine, suggesting that the efficacy of the vaccine was dependent on both CD4 þ and CD8 þ T cells. Lung metastasis of the tumor was also inhibited by vaccine treatment. Similarly, the percentages of tumor-specific Th1 cytokine production by CD4 þ and CD8 þ T cells in the spleen, tumor, and bronchoalveolar lavage were increased after vaccine treatment. Tumor-specific proliferation of CD4 þ and CD8 þ T cells was also promoted by the vaccine. Tetramer staining and cytotoxicity assay showed enhanced tumor-specific CD8 þ T-cell response after vaccine treatment. Therefore, the Salmonella tumor vaccine could activate both tumor-specific CD4 þ and CD8 þ T-cell responses. This vaccine strategy may be widely applicable to the development of oral or nasal vaccines against tumors.

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Zhao

Liu

et al. 2017

Cancer Immunology Research

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“…A DNA delivery system has the advantage, over traditional naked DNA vaccination, that bacteria protect the DNA vaccine from the environment until it reaches the macrophages, where the Salmonella is disrupted, releasing its intracellular plasmid cargo and enabling expression of the recombinant protein by the eukaryotic cell machinery. It was previously shown that oral immunization with this system is able to induce specific antibody and cellular responses, with Th1 and CD8 ϩ cell activation, as well as specific mucosal immunity (40)(41)(42).…”

Section: Discussionmentioning

confidence: 96%

Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge

et al. 2014

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In this work we immunized mice with DNA encoding full-length Tc52 or its amino-or carboxy-terminal (N-and C-term, respectively) domain carried by attenuated Salmonella as a DNA delivery system. As expected, Salmonella-mediated DNA delivery resulted in low antibody titers and a predominantly Th1 response, as shown by the ratio of IgG2a/IgG1-specific antibodies. Despite modest expression of Tc52 in trypomastigotes, the antibodies elicited by vaccination were able to mediate lysis of the trypomastigotes in the presence of complement and inhibit their invasion of mammal cells in vitro. The strongest functional activity was observed with sera from mice immunized with Salmonella carrying the N-term domain (SN-term), followed by Tc52 (STc52), and the C-term domain (SC-term). All immunized groups developed strong cellular responses, with predominant activation of Th1 cells. However, mice immunized with SN-term showed higher levels of interleukin-10 (IL-10), counterbalancing the inflammatory reaction, and also strong activation of Tc52-specific gamma interferon-positive (IFN-␥ ؉ ) CD8 ؉ T cells. In agreement with this, although all prototypes conferred protection against infection, immunization with SN-term promoted greater protection than that with SC-term for all parameters tested and slightly better protection than that with STc52, especially in the acute stage of infection. We conclude that the N-terminal domain of Tc52 is the section of the protein that confers maximal protection against infection and propose it as a promising candidate for vaccine development.

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“…Several strains of S. Typhimurium have been constructed for the purpose of tumor targeting and chemotherapy delivery, most mentionable being: A1 (Zhao et al, 2005)/A1-R Hiroshima et al, 2013;Hoffman, 2016;Hiroshima et al, 2014;Yano et al, 2014;Murakami et al, 2016;Kawaguchi et al, 2016), BRD509/BRD509E (Yoon et al, 2014;al-Ramadi et al, 2009), χ4550 (Saltzman et al, 1996), CRC2631 (Eisenstark et al, 2007), ΔppGpp (Jiang et al, 2013;Kim et al, 2015;Nguyen et al, 2010), LH340 (Zhang et al, 2007;VanCott et al, 1998;Jia et al, 2012), LVR01 (Grille et al, 2014), MvP728 (Manuel et al, 2011;Xu et al, 2014;Xiong et al, 2010), RE88 (Xiang et al, 2005;Lee et al, 2006;Qian et al, 2011), SA186 (Chirullo et al, 2015), SB824 (Roider et al, 2011), SL3261 (Lin et al, 2012;Ye et al, 2013), SL7207 (Jarosz et al, 2013;Li et al, 2013;Shi et al, 2016;Berger et al, 2013), YB1 (Li et al, 2017;Yu et al, 2015), and VNP20009 . VNP20009 was created by Low et al ) from strain 14028s through selection for hyperinvasion by chemical/UV mutagenesis.…”

Section: Introductionmentioning

confidence: 99%

Optimizing the restored chemotactic behavior of anticancer agent Salmonella enterica serovar Typhimurium VNP20009

Broadway

Suh

Behkam

et al. 2017

Journal of Biotechnology

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A B S T R A C TBacteria, including strains of Salmonella, have been researched and applied as therapeutic cancer agents for centuries. Salmonella are particularly of interest due to their facultative anaerobic nature, facilitating colonization of differentially oxygenated tumor regions. Additionally, Salmonella can be manipulated with relative ease, resulting in the ability to attenuate the pathogen or engineer vectors for drug delivery. It was recently discovered that the anti-cancer Salmonella enterica serovar Typhimurium strain VNP20009 is lacking in chemotactic ability, due to a non-synonymous single nucleotide polymorphism in cheY. Replacing the mutated copy of cheY with the wild-type sequence restored chemotaxis to 70% of the parental strain. We aimed to investigate further if chemotaxis of VNP20009 can be optimized. By restoring the gene msbB in VNP20009 cheY + , which confers attenuation by lipid A modification, we observed a 9% increase in swimming speed, 13% increase in swim plate performance, 19% increase in microfluidic device partitioning towards the attractant at the optimum concentration gradient, and mitigation of a non-motile cell subpopulation. We conclude that chemotaxis can be enhanced further but at the cost of changing one defining characteristic of VNP20009. A less compromised strain might be needed to employ for investigating bacterial chemotaxis in tumor interactions.

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Salmonella SL7207 application is the most effective DNA vaccine delivery method for successful tumor eradication in a murine model for neuroblastoma

Cited by 55 publications

References 49 publications

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge

Optimizing the restored chemotactic behavior of anticancer agent Salmonella enterica serovar Typhimurium VNP20009

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