Bacterial pathogens — a route to oral drug delivery

Dougan, Gordon; Chatfield, Steven N.; Roberts, Mark; Charles, Ian G.; Comerford, Sarah A.; Li, Li Jing; Fairweather, Neil F.

doi:10.1042/bst0180746

Cited by 2 publications

(2 citation statements)

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“…Bacteria that target inductive cells of the immune system are highly attractive candidates for vaccine delivery and have been developed as live vehicles for inducing protective responses to a wide variety of antigens. [102][103][104] Members of the Salmonella genus have been widely used as antigen carriers and several well-characterized safety attenuated strains are available. [105][106][107][108] Salmonella is capable of triggering both humoural and antigen-specific T-helper and cytotoxic responses.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Bacteria as vectors for gene therapy of cancer

et al. 2010

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Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to facilitate the production of therapeutic proteins. However, there is still much to be done before an efficient and safe gene medicine is achieved, primarily developing the means of targeting genes to tumors safely and efficiently. An emerging family of vectors involves bacteria of various genera. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally. Furthermore, invasive species can deliver heterologous genes intra-cellularly for tumor cell expression. Here, we review the use of bacteria as vehicles for gene therapy of cancer, detailing the mechanisms of action and successes at preclinical and clinical levels.

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Section: Therapeutic Strategiesmentioning

confidence: 99%

Bacteria as vectors for gene therapy of cancer

et al. 2010

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“…Many of these bacteria display regional tropisms often manifested as colonisation of specific mucosal surfaces or internal organs. Thus bacteria that target inductive cells of the immune system are highly attractive candidates for vaccine delivery and have in the past been developed as live vehicles for inducing protective responses to a wide variety of heterologously expressed antigens [3–5]. In this respect, bacteria‐based delivery systems would offer several advantages over currently used viral vectors [6,7].…”

Section: Introductionmentioning

confidence: 99%

Oral delivery of DNA vaccines using attenuatedSalmonella typhimuriumas carrier

Darji

Lage

Garbe

et al. 2000

FEMS Immunology &Amp; Medical Microbiology

109

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The efficacious delivery of eukaryotic expression plasmids to inductive cells of the immune system constitutes a key prerequisite for the generation of effective DNA vaccines. Here, we have explored the use of bacteria as vehicles to orally deliver expression plasmids. Attenuated Salmonella typhimurium aroA harbouring eukaryotic expression plasmids that encoded virulence factors of Listeria monocytogenes were administered orally to BALB/c mice. Strong cytotoxic and helper T cell responses as well as antibody production were elicited even after a single administration. Mice immunised four times with Salmonella that carried a eukaryotic expression plasmid encoding the secretory listerial protein listeriolysin were protected against a subsequent lethal challenge with this pathogen. A single dose was already partially protective. The efficiency of this vaccination procedure was due to transfer of the expression plasmid from the bacterial carrier to the mammalian host. Evidence for such an event could be obtained in vivo and in vitro. Expression of the desired antigen in various lymphoid tissues was already detectable 1 day after administration of the DNA vaccine and persisted for at least 1 month in spleen and mesenteric lymph nodes. Induction of cytotoxic and helper T cell responses was observed in all mouse strains tested including outbred strains whereas antibodies were mainly detected in BALB/c. Furthermore, we could show that immunogenicity could be improved by increasing the invasiveness of the bacterial carrier.

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Bacterial pathogens — a route to oral drug delivery

Cited by 2 publications

References 0 publications

Bacteria as vectors for gene therapy of cancer

Bacteria as vectors for gene therapy of cancer

Oral delivery of DNA vaccines using attenuatedSalmonella typhimuriumas carrier

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