Glioblastoma (GBM) remains one of the most difficult brain tumours to treat, with a lack of effective therapeutic options for patients. In an attempt overcome this challenge, the team at Duke selected a non-toxic strain of Salmonella to detect GBM tumour cells and exert anti-tumour properties.
To ensure that the bacteria reached the tumour sites in animal models, the strain of bacteria used was deficient in a crucial enzyme called purine, which is required by the bacteria for growth and survival. Tumours are abundant in this enzyme, so upon injection the bacteria were programmed to seek out the tumour and multiply at its site.
Additionally, the researchers genetically modified the bacteria so that they carried specific proteins to induce tumour killing mechanisms in the animal models. They were designed to carry p53, a multi-functional protein that triggers the self-destruction of cells with faulty DNA (a biological process called apoptosis), as well as a protein called Azurin. Azurin also induces apoptosis, without being toxic to non-cancerous, healthy cells.
Ravi Bellamkonda, Vinik Dean of Duke's Pratt School of Engineering and corresponding author of the study said, “A major challenge in treating gliomas is that the tumour is dispersed with no clear edge, making them difficult to completely surgically remove. So designing bacteria to actively move and seek out these distributed tumours, and express their anti-tumour proteins only in hypoxic, purine rich tumour regions is exciting.
“And because their natural toxicity has been deactivated, they don't cause an immunological response. At the doses we used in the experiments, they were naturally cleared once they'd killed the tumours, effectively destroying their own food source."
The study found that the treatment very encouragingly increased the overall survival in the treated animal models by 19%, compared to 0% in models that had not been injected with the bacteria. Whilst these are very early stage findings, this therapeutic response shows hope of this model as a potential clinically viable treatment.
The researchers now aim to carry out more studies by designing the bacteria to produce different drugs that cause stronger reactions in the tumour.
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