use of clostridial spores for cancer treatment

• Published in: Journal of applied microbiology 2006-09, Vol.101 (3), p.571-578
• Main Authors: Barbé, S, Mellaert, L. Van, Anné, J
• Format: Article
• Language: English
• Subjects: anaerobes; Biological and medical sciences; cancer treatment; Clostridium; Clostridium - physiology; Fundamental and applied biological sciences. Psychology; Genetic Therapy - methods; Genetic Vectors - therapeutic use; Humans; hypoxia; Hypoxia - metabolism; Microbiology; Necrosis; Neoplasms - microbiology; Neoplasms - pathology; Neoplasms - therapy; Oxygen - physiology; Prodrugs - metabolism; Recombination, Genetic; solid tumour; spores; Spores, Bacterial - physiology
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/j.1365-2672.2006.02886.x

Hypoxic/necrotic regions, absent in normal tissues, can be exploited to target tumours in cancer therapy using nonpathogenic strains of the bacterial genus Clostridium. Following administration of Clostridium spores to tumour-bearing organisms, these spores can only germinate within the hypoxic/necrotic regions of solid tumours, proving their exquisite selectivity. Low oxygen tension is a common feature of solid tumours, which may arise from the unique physiological environment, generated to a large extent by the abnormal tumour vasculature, and provides as such a niche for anaerobic bacteria. Some clostridia tested clearly showed innate oncolytic activity, but they could not completely eradicate the tumour. Recombinant clostridia producing prodrug-converting enzymes or cytokines resulted in the production of such proteins solely within the tumour, and where applicable, could convert the prodrug in a toxic compound. Moreover, in some cases, tumour eradication or tumour control could be observed. This review brings an overview of the relative successes and failures of the Clostridium-directed tumour therapy with both wild-type strains and strains producing proteins useful in antitumour therapy.