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Tumour-targeting bacteria engineered to fight cancer.

ABSTRACT: Recent advances in targeted therapy and immunotherapy have once again raised the hope that a cure might be within reach for many cancer types. Yet, most late-stage cancers are either insensitive to the therapies to begin with or develop resistance later. Therapy with live tumour-targeting bacteria provides a unique option to meet these challenges. Compared with most other therapeutics, the effectiveness of tumour-targeting bacteria is not directly affected by the 'genetic makeup' of a tumour. Bacteria initiate their direct antitumour effects from deep within the tumour, followed by innate and adaptive antitumour immune responses. As microscopic 'robotic factories', bacterial vectors can be reprogrammed following simple genetic rules or sophisticated synthetic bioengineering principles to produce and deliver anticancer agents on the basis of clinical needs. Therapeutic approaches using live tumour-targeting bacteria can either be applied as a monotherapy or complement other anticancer therapies to achieve better clinical outcomes. In this Review, we summarize the potential benefits and challenges of this approach. We discuss how live bacteria selectively induce tumour regression and provide examples to illustrate different ways to engineer bacteria for improved safety and efficacy. Finally, we share our experience and insights on oncology clinical trials with tumour-targeting bacteria, including a discussion of the regulatory issues.

SUBMITTER: Zhou S

PROVIDER: S-EPMC6902869 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Tumour-targeting bacteria engineered to fight cancer.

Zhou Shibin S Gravekamp Claudia C Bermudes David D Liu Ke K

Nature reviews. Cancer 20181201 12

Recent advances in targeted therapy and immunotherapy have once again raised the hope that a cure might be within reach for many cancer types. Yet, most late-stage cancers are either insensitive to the therapies to begin with or develop resistance later. Therapy with live tumour-targeting bacteria provides a unique option to meet these challenges. Compared with most other therapeutics, the effectiveness of tumour-targeting bacteria is not directly affected by the 'genetic makeup' of a tumour. Ba ...[more]

PMID: 30405213

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Project description:Conventional therapies for cancer eradication like surgery, radiotherapy, and chemotherapy, even though most widely used, still suffer from some disappointing outcomes. The limitations of these therapies during cancer recurrence and metastasis demonstrate the need for better alternatives. Some bacteria preferentially colonize and proliferate inside tumor mass; thus these bacteria can be used as ideal candidates to deliver antitumor therapeutic agents. The bacteria like Bacillus spp., Clostridium spp., E. coli, Listeria spp., and Salmonella spp. can be reprogrammed to produce, transport, and deliver anticancer agents, eg, cytotoxic agents, prodrug converting enzymes, immunomodulators, tumor stroma targeting agents, siRNA, and drug-loaded nanoformulations based on clinical requirements. In addition, these bacteria can be genetically modified to express various functional proteins and targeting ligands that can enhance the targeting approach and controlled drug-delivery. Low tumor-targeting and weak penetration power deep inside the tumor mass limits the use of anticancer drug-nanoformulations. By using anticancer drug nanoformulations and other therapeutic payloads in combination with antitumor bacteria, it makes a synergistic effect against cancer by overcoming the individual limitations. The tumor-targeting bacteria can be either used as a monotherapy or in addition with other anticancer therapies like photothermal therapy, photodynamic therapy, and magnetic field therapy to accomplish better clinical outcomes. The toxicity issues on normal tissues is the main concern regarding the use of engineered antitumor bacteria, which requires deeper research. In this article, the mechanism by which bacteria sense tumor microenvironment, role of some anticancer agents, and the recent advancement of engineering bacteria with different therapeutic payloads to combat cancers has been reviewed. In addition, future prospective and some clinical trials are also discussed.

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Tumour-targeting bacteria engineered to fight cancer.

Publications

Tumour-targeting bacteria engineered to fight cancer.

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