Harmless soil bacteria used to deliver drugs direct to tumour cells
8 September 2011
A genetically altered soil bacteria that specifically targets
tumours could soon be used as a vehicle to deliver drugs to destroy
The therapy uses Clostridium sporogenes, a bacterium
that is widespread in the soil. Spores of the bacterium are injected
into patients and only grow in solid tumours, where a specific
bacterial enzyme is produced.
An anti-cancer drug is injected separately into the patient in an
inactive 'pro-drug' form. When the pro-drug reaches the site of the
tumour, the bacterial enzyme activates the drug, allowing it to
destroy only the cells in its vicinity, the tumour cells.
Researchers at the University of Nottingham and the University of
Maastricht have now overcome the hurdles that have so far prevented
this therapy from entering clinical trials. They have introduced a
gene for a much-improved version of the enzyme into the C.
sporogenes DNA. The improved enzyme can now be produced in far
greater quantities in the tumour than previous versions, and is more
efficient at converting the pro-drug into its active form. The
technique is expected to be tested in clinical trials with cancer
patients in 2013.
A fundamental requirement for any new cancer therapy is the
ability to target cancer cells while excluding healthy cells.
Professor Nigel Minton, who is leading the research, explains how
this therapy naturally fulfils this need, "Clostridia are an ancient
group of bacteria that evolved on the planet before it had an
oxygen-rich atmosphere and so they thrive in low oxygen conditions.
"When Clostridia spores are injected into a cancer patient, they
will only grow in oxygen-depleted environments, ie the centre of
solid tumours. This is a totally natural phenomenon, which requires
no fundamental alterations and is exquisitely specific. We can
exploit this specificity to kill tumour cells but leave healthy
The research may ultimately lead to a simple and safe procedure
for curing a wide range of solid tumours. "This therapy will kill
all types of tumour cell. The treatment is superior to a surgical
procedure, especially for patients at high risk or with difficult
tumour locations," explained Professor Minton.
"We anticipate that the strain we have developed will be used in
a clinical trial in 2013 led by Jan Theys and Philippe Lambin at the
University of Maastricht in The Netherlands. A successful outcome
could lead to its adoption as a frontline therapy for treating solid
tumours. If the approach is successfully combined with more
traditional approaches this could increase our chance of winning the
battle against cancerous tumours."
The research was presented as a poster at the Society for General
Microbiology's Autumn Conference 2011 in York this week.