Potent and Tumor specific: Arming Bacteria With Therapeutic Proteins

Dessel, Nele Van; Swofford, Charles A.; Forbes, Neil S.

doi:10.4155/tde.14.113

Cited by 42 publications

(24 citation statements)

References 122 publications

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“…Second, as a biosafety control we aimed to develop a nitroreductase that can effectively activate the clinically approved 5-nitroimidazole prodrug metronidazole; safe clinical use of bacterial delivery vectors such as Clostridium sporogenes necessitates the use of antibiotics (Mowday et al, 2016a), and metronidazole is the most commonly used antibiotic for treatment of clostridial and other anaerobic bacterial infections (Lö fmark et al, 2010). Other obligate and facultative anaerobes, including E. coli, Bifidobacterium, Listeria, and Salmonella strains have been extensively studied as gene delivery vectors for GDEPT, and offer enormous promise due to their specificity and exceptionally high levels of tumor colonization (Van Dessel et al, 2015). It would, therefore, be highly desirable to engineer an oxygen-independent GDEPT nitroreductase to confer hypersensitivity to this antibiotic.…”

Section: Introductionmentioning

confidence: 99%

Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy

Copp

Mowday

Williams

et al. 2017

Cell Chemical Biology

115

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Gene-directed enzyme-prodrug therapy (GDEPT) is a promising anti-cancer strategy. However, inadequate prodrugs, inefficient prodrug activation, and a lack of non-invasive imaging capabilities have hindered clinical progression. To address these issues, we used a high-throughput Escherichia coli platform to evolve the multifunctional nitroreductase E. coli NfsA for improved activation of a promising next-generation prodrug, PR-104A, as well as clinically relevant nitro-masked positron emission tomography-imaging probes EF5 and HX4, thereby addressing a critical and unmet need for non-invasive bioimaging in nitroreductase GDEPT. The evolved variant performed better in E. coli than in human cells, suggesting optimal usefulness in bacterial rather than viral GDEPT vectors, and highlighting the influence of intracellular environs on enzyme function and the shaping of promiscuous enzyme activities within the "black box" of in vivo evolution. We provide evidence that the dominant contribution to improved PR-104A activity was enhanced affinity for the prodrug over-competing intracellular substrates.

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Section: Introductionmentioning

confidence: 99%

Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy

Copp

Mowday

Williams

et al. 2017

Cell Chemical Biology

115

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“…This mode of communication is referred to as quorum sensing (QS). The regulation of gene expression can also be controlled by these QS molecules [ 72 ]. The application of QS phenomenon in cancer treatment has been discussed in detail in Section 2.6 .…”

Section: Mechanism Of Tumor Suppressionmentioning

confidence: 99%

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

Sawant

Patil

Gupta

et al. 2020

IJMS

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Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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“…e easier access to genetic manipulation strategies offers new opportunities to establish unique technologies both in cancer therapeutics and in cancer diagnosis [58,59]. Nonpathogenic strains like E. coli Nissle 1917 can target and reproduce within the tumor cells as well as necrotic tissues [60].…”

Section: Anticancer Erapeuticsmentioning

confidence: 99%

The Prospects for the Therapeutic Implications of Genetically Engineered Probiotics

Mazhar

Afzal

Almatroudi

et al. 2020

Journal of Food Quality

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The interest in the therapeutic use of probiotic microorganisms has been increased during the last decade although the doubts have ascended about the probiotics mainly because their beneficial effects are not fully understood, and, in many cases, their usefulness has not been validated in clinical trials. Consequently, the notion got a considerable interest in those strains having proven probiotic potential to be engineered for improvement in their beneficial features. The process of genetic engineering can also be used for probiotic strains for the reversion of antimicrobial resistance and other modifications for their safer and effective human applications. The lactic acid bacilli are predominantly opposite as they already have gained attention owing to their health-promoting benefits and their safety for human consumption; therefore, their use, especially as a delivery agent of vaccines and drugs, is gaining attention. The tailoring of probiotic strains will not only improve the data regarding the probiotic potential of these strains but also clinch the doubts concerning these probiotics. This article focuses on the approaches of bioengineered probiotics and discusses the potential prospects for their therapeutic applications including immunomodulation, cognitive health, and anticancer therapeutics.

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Potent and Tumor specific: Arming Bacteria With Therapeutic Proteins

Cited by 42 publications

References 122 publications

Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy

Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

The Prospects for the Therapeutic Implications of Genetically Engineered Probiotics

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