Bacterial targeted tumour therapy-dawn of a new era.
Original observation of patients' spontaneous recovery from advanced tumours after an infection or a "fever" inspired extensive research. As a result, Coley's toxin for the therapy of sarcomas and live Bacillus Calmette-Guerin (BCG) for bladder cancer were born. In addition, three genera of anaerobic bacteria have been shown to specifically and preferentially target solid tumours and cause significant tumour lyses. Initial research had focused on determining the best tumour colonizing bacteria, and assessing the therapeutic efficacy of different strategies either as a single or combination treatment modalities. However, although clinical trials were carried out as early as the 1960s, lack of complete tumour lyses with injection of Clostridial spores had limited their further use. Recent progress in the field has highlighted the rapid development of new tools for genetic manipulation of Clostridia which have otherwise been a hurdle for a long time, such as plasmid transformation using electroporation that bore the problems of inefficiency, instability and plasmid loss. A new Clostridium strain, C. novyi-NT made apathogenic by genetic modification, is under clinical trials. New genetic engineering tools, such as the group II intron has shown promise for genetic manipulation of bacteria and forecast the dawn of a new era for a tumour-targeted bacterial vector system for gene therapy of solid tumours. In this review we will discuss the potential of genetically manipulated bacteria that will usher in the new era of bacterial therapy for solid tumours, and highlight strategies and tools used to improve the bacterial oncolytic capability.
Department of Medicine, University of Queensland, Prince Charles Hospital, Brisbane, Qld 4032, Australia. d.wei@uq.edu.au <d.wei@uq.edu.au>
Ming Q
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Asferd
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Mengesha
David
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Jozef
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Anné
D000818:Animals; D001421:Bacteria, Anaerobic / Q000235:genetics* / Q000472:pathogenicity; D015687:Cell Hypoxia; D003013:Clostridium / Q000235:genetics* / Q000472:pathogenicity; D004269:DNA, Bacterial / Q000627:therapeutic use*; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007438:Introns; D009336:Necrosis; D009369:Neoplasms / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D013171:Spores, Bacterial
D004269:DNA, Bacterial