The use of clostridial spores for cancer treatment.
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.
Barbé
S
S
Laboratory of Bacteriology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium.
Van Mellaert
L
L
Anné
J
J
D003013:Clostridium / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D010100:Oxygen / Q000502:physiology; D011355:Prodrugs / Q000378:metabolism; D011995:Recombination, Genetic; D013171:Spores, Bacterial / Q000502:physiology
D011355:Prodrugs; D010100:Oxygen