Probiotic bacteria that have been engineered to deliver drugs can significantly reduce tumours after a single dose.
Developed at Columbia University in New York, US, the approach is part of a family of cancer treatments known as immunotherapy, which use the patient’s own immune system to fight the cancer.
The bacteria work by releasing drugs known as ‘checkpoint inhibitors’, which target the body’s immune system. One of the immune system’s key jobs is to be able to tell the difference between normal cells and foreign cells, such as cancerous ones.
The immune system’s response is regulated by ‘checkpoints’ – molecules that have to be activated or deactivated in order for the immune system to go into attack mode. Some cancers are able to protect themselves from attack by simulating these checkpoints, so checkpoint inhibitor drugs are designed to target the checkpoints, removing the brakes on the immune system.
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Although these drugs have had some success, they currently lead to side effects in a high proportion of cancer patients. Researchers led by Prof Tal Danino at Columbia have now engineered bacteria that can enter tumours and deliver the drugs directly.
“We wanted to engineer a safe probiotic vehicle capable of delivering immune checkpoint therapies locally to minimise side effects,” said Danino.
The team used their biotechnology in mice with lymphoma and colorectal cancer, targeting two checkpoints known as ‘PD-L1’ and ‘CTLA-4’. The programmed bacteria were able to find tumours and grow inside them, constantly releasing drugs in the process.
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The researchers found that their approach was more effective than current treatments at tackling the tumours, and could clear tumours after a single dose.
“We’ve demonstrated that one dose of our probiotic therapy results in continuous localised drug release and clearance of the bacteria population once tumours have cleared,” said Columbia PhD student Candice Gurbatri. “These elements could be particularly beneficial in a clinical setting, where patients want and need minimally invasive and self-sustained therapies.”