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Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems

Solid tumours account for 90% of all cancers. Gene therapy represents a potential new modality for their treatment. Up to now, several approaches have been developed, but the most efficient ones are the viral vector based gene therapy systems. However, viral vectors suffer from several deficiencies:...

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Autores principales: Wei, Ming Q, Ren, Ruimei, Good, David, Anné, Jozef
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267465/
https://www.ncbi.nlm.nih.gov/pubmed/18279524
http://dx.doi.org/10.1186/1479-0556-6-8
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author Wei, Ming Q
Ren, Ruimei
Good, David
Anné, Jozef
author_facet Wei, Ming Q
Ren, Ruimei
Good, David
Anné, Jozef
author_sort Wei, Ming Q
collection PubMed
description Solid tumours account for 90% of all cancers. Gene therapy represents a potential new modality for their treatment. Up to now, several approaches have been developed, but the most efficient ones are the viral vector based gene therapy systems. However, viral vectors suffer from several deficiencies: firstly most vectors currently in use require intratumoural injection to elicit an effect. This is far from ideal as many tumours are inaccessible and many may have already spread to other parts of the body, making them difficult to locate and inject gene therapy vectors into. Second, because of cell heterogeneity within a given cancer, the vectors do not efficiently enter and kill every cancer cell. Third, hypoxia, a prevalent characteristic feature of most solid tumours, reduces the ability of the viral vectors to function and decreases viral gene expression and production. Consequently, a proportion of the tumour is left unaffected, from which tumour regrowth occurs. Thus, cancer gene therapy has yet to realise its full potential. The facultative or obligate anaerobic bacteria have been shown to selectively colonise and regerminate in solid tumours when delivered systemically. Among them, the clostridial spores were easy to produce, stable to store and safe to use as well as having extensive oncolytic ability. However, research in animals and humans has shown that oncolysis was almost always interrupted sharply at the outer rim of the viable tumour tissue where the blood supply was sufficient. These clostridial spores, though, could serve as "Trojan horse" for cancer gene therapy. Indeed, various spores harbouring genes for cancerstatic factors, prodrug enzymes, or proteins or cytokines had endowed with additional tumour-killing capability. Furthermore, combination of these "Trojan horses" with conventional chemotherapy or radiation therapies often significantly perform better, resulting in the "cure" of solid tumours in a high percentage of animals. It is, thus, not too difficult to predict the potential outcomes for the use of clostridial spores as "Trojan horse" vectors for oncolytic therapy when compared with viral vector-mediated cancer therapy for it be replication-deficient or competent. However, to move the "Trojan horse" to a clinic, though, additional requirements need to be satisfied (i) target tumours only and not anywhere else, and (ii) be able to completely kill primary tumours as well as metastases. Current technologies are in place to achieve these goals.
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spelling pubmed-22674652008-03-14 Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems Wei, Ming Q Ren, Ruimei Good, David Anné, Jozef Genet Vaccines Ther Review Solid tumours account for 90% of all cancers. Gene therapy represents a potential new modality for their treatment. Up to now, several approaches have been developed, but the most efficient ones are the viral vector based gene therapy systems. However, viral vectors suffer from several deficiencies: firstly most vectors currently in use require intratumoural injection to elicit an effect. This is far from ideal as many tumours are inaccessible and many may have already spread to other parts of the body, making them difficult to locate and inject gene therapy vectors into. Second, because of cell heterogeneity within a given cancer, the vectors do not efficiently enter and kill every cancer cell. Third, hypoxia, a prevalent characteristic feature of most solid tumours, reduces the ability of the viral vectors to function and decreases viral gene expression and production. Consequently, a proportion of the tumour is left unaffected, from which tumour regrowth occurs. Thus, cancer gene therapy has yet to realise its full potential. The facultative or obligate anaerobic bacteria have been shown to selectively colonise and regerminate in solid tumours when delivered systemically. Among them, the clostridial spores were easy to produce, stable to store and safe to use as well as having extensive oncolytic ability. However, research in animals and humans has shown that oncolysis was almost always interrupted sharply at the outer rim of the viable tumour tissue where the blood supply was sufficient. These clostridial spores, though, could serve as "Trojan horse" for cancer gene therapy. Indeed, various spores harbouring genes for cancerstatic factors, prodrug enzymes, or proteins or cytokines had endowed with additional tumour-killing capability. Furthermore, combination of these "Trojan horses" with conventional chemotherapy or radiation therapies often significantly perform better, resulting in the "cure" of solid tumours in a high percentage of animals. It is, thus, not too difficult to predict the potential outcomes for the use of clostridial spores as "Trojan horse" vectors for oncolytic therapy when compared with viral vector-mediated cancer therapy for it be replication-deficient or competent. However, to move the "Trojan horse" to a clinic, though, additional requirements need to be satisfied (i) target tumours only and not anywhere else, and (ii) be able to completely kill primary tumours as well as metastases. Current technologies are in place to achieve these goals. BioMed Central 2008-02-17 /pmc/articles/PMC2267465/ /pubmed/18279524 http://dx.doi.org/10.1186/1479-0556-6-8 Text en Copyright © 2008 Wei et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Wei, Ming Q
Ren, Ruimei
Good, David
Anné, Jozef
Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems
title Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems
title_full Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems
title_fullStr Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems
title_full_unstemmed Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems
title_short Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems
title_sort clostridial spores as live 'trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267465/
https://www.ncbi.nlm.nih.gov/pubmed/18279524
http://dx.doi.org/10.1186/1479-0556-6-8
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