Details

Autor(en) / Beteiligte

• Minton, Nigel P
• Mauchline, Margaret L
• Lemmon, Marylin J
• Brehm, John K
• Fox, Mary
• Michael, N.Paul
• Giaccia, Amato
• Brown, J.Martin

Titel

Chemotherapeutic tumour targeting using clostridial spores

Ist Teil von

• FEMS microbiology reviews, 1995-10, Vol.17 (3), p.357-364

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

1995

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• : The toxicity associated with conventional cancer chemotherapy is primarily due to a lack of specificity for tumour cells. In contrast, intravenously injected clostridial spores exhibit a remarkable specificity for tumours. This is because, following their administration, clostridial spores become exclusively localised to, and germinate in, the hypoxic/necrotic tissue of tumours. This unique property could be exploited to deliver therapeutic agents to tumours. In particular, genetic engineering could be used to endow a suitable clostridial host with the capacity to produce an enzyme within the tumour which can metabolise a systematically introduced, non‐toxic prodrug into a toxic metabolite. The feasibility of this strategy (clostridial‐directed enzyme prodrug therapy, CDEPT) has been demonstrated by cloning the Escherichia coli B gene encoding nitroreductase (an enzyme which converts the prodrug CB1954 to a highly toxic bifunctional alkylating agent) into a clostridial expression vector and introducing the resultant plasmid into Clostridium beijerinckii (formerly C. acetobutylicum) NCIMB 8052. The gene was efficiently expressed, with recombinant nitroreductase representing 8% of the cell soluble protein. Following the intravenous injection of the recombinant spores into mice, tumour lysates have been shown, by Western blots, to contain the E. coli‐derived enzyme.