Using bacteria to target an aggressive form of prostate cancer

Grant information

Reference: RIA24-ST2-005
Lead researcher: Dr Terry Bilverstone and Professor Francesco Crea
Institution: The Open University
Award: £99,873
Duration: 24 months

What you need to know

• Neuroendocrine prostate cancer is an aggressive form of the disease. It can develop when prostate cancer stops responding to hormone therapy, and men urgently need new treatment options.

• The researchers will test whether bacteria that can grow in the low-oxygen conditions inside cancers can find and destroy cancer cells.

• They’ll also adapt the bacteria to make a cancer-killing protein inside the cancer. In future, this could help concentrate treatment where it’s needed and limit harmful effects elsewhere in the body.

Why are we funding this research?

Neuroendocrine prostate cancer can develop when prostate cancer stops responding to hormone therapy. It can spread quickly and doesn’t respond to the treatments we usually use for prostate cancer. Men who develop it have very limited options, so we urgently need new approaches.

These cancers contain areas with very little oxygen. The researchers want to turn this feature into a target. They’ll use a bacterium called Clostridium novyi-NT, which can grow in low-oxygen areas inside some cancers. Scientists have studied it as an experimental treatment for other cancers, but not specifically for neuroendocrine prostate cancer.

The researchers will also explore whether the bacteria can carry treatments directly into the cancer. Their earlier work found that a protein made by the immune system, called tumour necrosis factor alpha, can kill neuroendocrine prostate cancer cells. But giving enough of this protein throughout the body could be too toxic. Making it inside the cancer could offer a more targeted way to use it.

What will the researchers do?

First, the researchers will test the bacteria against several types of neuroendocrine prostate cancer cells in the lab. They’ll grow the cells in low-oxygen conditions like those found inside these cancers, then add the bacteria. They’ll measure whether the cancer cells keep growing or die and study how the bacteria interact with them.

They’ll compare the results with chemotherapy and another experimental method for delivering tumour necrosis factor alpha. This will help them judge how the bacterial approach performs against other possible treatments.

Next, the team will test the bacteria in mice with neuroendocrine prostate cancer. They’ll inject bacterial spores directly into the cancer and compare the results with mice that don’t receive the treatment. They’ll check whether the cancer continues to grow, whether the spores turn into bacteria inside it and how the immune cells around the cancer respond. They’ll also monitor the mice carefully for unwanted effects.

In the second part of the project, the researchers will adapt the bacteria so they can make tumour necrosis factor alpha. They’ll add the genetic instructions for producing the protein and test different ways to control how much is made and help the bacteria release it.

Finally, they’ll check whether the adapted bacteria can make and release the protein, and whether it kills neuroendocrine prostate cancer cells in the lab.

This is an early-stage pilot project. The team won’t test the adapted, protein-producing bacteria in mice during this study. If the lab results are promising, further research would be needed to test this part of the approach in animals.

How will this benefit men?

Men with neuroendocrine prostate cancer currently have very limited treatment options. This project could provide the first evidence of whether Clostridium novyi-NT is worth developing specifically for this aggressive form of the disease.

If the approach works, the bacteria could eventually have two roles: destroying cancer cells themselves and carrying treatment directly into the cancer. This could be especially useful for treatments that show promise against cancer cells but are too toxic to give throughout the body.

Although this research is at a very early stage – it doesn’t involve men with prostate cancer and won’t produce a treatment ready for use – promising results would support larger animal studies to learn more about how safe and effective the approach is, ahead of any potential clinical trials.