Salmonella as a biological “Trojan horse” for neoplasia: Future possibilities including brain cancer

Mlynarczyk, Gregory S.A.; Berg, Carrie A.; Withrock, Isabelle C.; Fick, Meghan Elizabeth; Anderson, Stephen J.; Laboissonniere, Lauren A.; Jefferson, Matthew; Brewer, Matthew T.; Stock, Michelle L.; Lange, Jennifer K.; Luna, K.C.; Acharya, Sreemoyee; Kanuri, Sriharsha; Sharma, Shaunik; Kondru, Naveen; McCormack, Garrett R.; Carlson, Steve A.

doi:10.1016/j.mehy.2014.06.009

Cited by 3 publications

(1 citation statement)

References 23 publications

(26 reference statements)

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“…Unlike bacterial minicells however, live replication competent bacteria have the potential to persist in tumors for weeks, continuously producing an anticancer agent or stimulating immune responses, which may represent a significant therapeutic advantage. Furthermore, some Salmonella strains such as Salmonella saintpaul isolate (SstpNPG) can reach the brain and have been proposed as a vector for treating brain tumors (Mlynarczyk et al, 2014). This approach may be of special use since some brain tumors overexpress EGFR and may, therefore, be amenable to Salmonella expressing EGFR-targeted therapeutics.…”

Section: Discussionmentioning

confidence: 99%

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

Quintero

Carrafa²,

Vincent³

et al. 2016

Biotech & Bioengineering

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Tumor-targeted Salmonella VNP20009 preferentially replicate within tumor tissue and partially suppress tumor growth in murine tumor models. These Salmonella have the ability to locally induce apoptosis when they are in direct contact with cancer cells but they lack significant bystander killing, which may correlate with their overall lack of antitumor activity in human clinical studies. In order to compensate for this deficiency without enhancing overall toxicity, we engineered the bacteria to express epidermal growth factor receptor (EGFR)-targeted cytotoxic proteins that are released into the extracellular milieu. In this study, we demonstrate the ability of the Salmonella strain VNP20009 to produce three different forms of the Pseudomonas exotoxin A (ToxA) chimeric with a tumor growth factor alpha (TGFα) which results in its producing culture supernatants that are cytotoxic and induce apoptosis in EGFR positive cancer cells as measured by the tetrazolium dye reduction, and Rhodamine 123 and JC-10 mitochondrial depolarization assays. In addition, exchange of the ToxA REDLK endoplasmic reticulum retention signal for KDEL and co-expression of the ColE3 lysis protein resulted in an overall increased cytotoxicity compared to the wild type toxin. This approach has the potential to significantly enhance the antitumor activity of VNP20009 while maintaining its previously established safety profile.

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Section: Discussionmentioning

confidence: 99%

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

Quintero

Carrafa²,

Vincent³

et al. 2016

Biotech & Bioengineering

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Microbiome as an Immunological Modifier

Kumar

Singh

Murugesan

et al. 2019

Biomarkers for Immunotherapy of Cancer

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Microbes and Cancer

Dzutsev

Badger

Perez‐Chanona

et al. 2017

Annu. Rev. Immunol.

208

181

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Commensal microorganisms (the microbiota) live on all the surface barriers of our body and are particularly abundant and diverse in the distal gut. The microbiota and its larger host represent a metaorganism in which the cross talk between microbes and host cells is necessary for health, survival, and regulation of physiological functions locally, at the barrier level, and systemically. The ancestral molecular and cellular mechanisms stemming from the earliest interactions between prokaryotes and eukaryotes have evolved to mediate microbe-dependent host physiology and tissue homeostasis, including innate and adaptive resistance to infections and tissue repair. Mostly because of its effects on metabolism, cellular proliferation, inflammation, and immunity, the microbiota regulates cancer at the level of predisposing conditions, initiation, genetic instability, susceptibility to host immune response, progression, comorbidity, and response to therapy. Here, we review the mechanisms underlying the interaction of the microbiota with cancer and the evidence suggesting that the microbiota could be targeted to improve therapy while attenuating adverse reactions.

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Salmonella as a biological “Trojan horse” for neoplasia: Future possibilities including brain cancer

Cited by 3 publications

References 23 publications

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

Microbiome as an Immunological Modifier

Microbes and Cancer

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