The genetically modified bacterium, Clostridium novyi-NT (C.novyi-NT) has been found to have a special taste for the oxygen-starved regions found at the centres of large cancerous growths by researchers at the John Hopkins Kimmel Cancer Centre. The bacterium also secretes a protein that opens up anti-cancer therapies encapsulated in fatty capsules, known as liposomes, turning the normal slow-release mechanism into a targeted chemotherapy bomb.
When tumours grow to a size greater than that of a pinhead the centre of the cancerous growth becomes starved of oxygen due to the lack of organized blood capillaries feeding the growth.
The genetically modified C.novyi-NT bacterium thrives in these oxygen-deficient areas, which are unique to cancerous growths, and starts to kill the tumour from the inside out. Normal surrounding cells were largely unaffected as were the exterior of the tumours as the bacteria don't like the more oxygen rich conditions.
The modified bacteria have been found to be relatively harmless and were entered into Phase I clinical trials in July at the John Hopkins Hospital in Baltimore. Their unmodified counterparts produce poisons that have killed some humans and cattle when introduced to the bloodstream.
When the bacteria were administered to a sample of 100 mice alongside liposome 'packaged' chemotherapy drugs, such as doxorubicin or irinotecan, both large and small tumours were completely destroyed and more than two thirds of the mice were permanently cured.
The synergistic mechanism of action arises because the bacteria secretes a protein, dubbed, by the lead author of the study Dr Ian Cheong, as liposomase, which disrupts the lipid packaging of the drug and delivers the payload.
Talking to DrugResearcher.com, Cheong said: "the tumour-specific release allows us to administer a higher drug dose while actually decreasing the collateral damage to healthy tissue compared to if we had administered the free drug alone."
"Since this method is not limited to any one particular tumor type or drug, its potential to 'rescue' toxic drugs and improve already successful drugs is therefore very broad."
The encapsulated drugs naturally gravitate towards the tumours because they are too large to fit through the series of tightly woven blood vessels that surround normal tissue but are small enough to fit through the irregular blood vessel systems that surround tumours.
Cheong continued: "Ironically, the larger the tumour the better; the largest tumours we've treated in mice are smaller than the smallest tumours that are routinely detected in humans."
This liposomase also has the potential to work in a similar manner for other targeted treatments if the protein was attached to site-targeting antibodies or by attaching it to gene therapies.
The genome for the bacteria was recently decoded by the Hopkins team and according to Shibin Zhou, assistant professor of oncology at the John Hopkins Kimmel Cancer Centre, "was instrumental in identifying liposomase and will help improve our bacterial based therapies."