Tumour-hunting stem cells beat back brain cancer

03 February 2017

Glioblastoma_-_MR_coronal_with_contrast.jpg

Gliobastoma (astrocytoma) WHO grade IV - MRI coronal view, post contrast. 15 year old boy.

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Stem cells made from adult skin and programmed to hunt down tumours have been developed by scientists in the US.

In ways that scientists are still working out, certain types of stem cell are naturally drawn to sites of cancer spread, probably in response to attractive signals that leach out of the tumour. So scientists have begun to exploit this homing instinct by loading the stem cells with anticancer-cargoes that are then delivered to the tumour as the stem cells burrow their way in.

In tests on mice with glioblastoma, a deadly form a brain cancer, tumours treated this way shrank by up to 90%, and phase 1 clinical trials are now underway in human subjects. However, these trials have relied heavily on stem cells made from other patients and are therefore not a genetic match for the individual undergoing treatment.

This could carry risks and also limits the duration of the therapeutic effect that these cells can effect before they are removed by the immune system.

Now University of North Carolina scientist Juli Bago and her colleagues have come up with a way to turn a patient's own skin cells into the neural stem cells (NSCs) known to be highly effective at tracking down cancer.

With a rapidly progressive disease like glioblastoma time is of the essence. Thankfully these cells can be made within just 4 days and the new technique means that a patient can be injected with cells that are genetically matched with themselves.

The technique is described this week in the journal Science Translational Medicine. Human skin cells known as fibroblasts were re-programmed in culture by adding a cell signal called SOX2 and providing a combination of NSC-provoking factors in the growth medium. This triggered the fibroblasts to switch from skin cells to NSCs.

Mixed with glioblastoma cells in culture, the newly reprogrammed NSCs moved rapidly towards and inveigled their way into tumour. To see whether the NSCs were capable of killing off the cancer cells the team tested two approaches.

First they programmed the cells to produce a suicide signal called TRAIL, which triggers adjacent cells to die. Compared with control mice, the mice that received the TRAIL-expressing NSCs had 50 fold lower levels of tumour in their brains 24 days later.

The team also engineered their NSCs to produce an enzyme called thymidine kinase (TK), which can convert a harmless drug called ganciclovir into a toxic active form that destroys growing cells. Test mice that received the NSCs and the ganciclovir drug had 20-fold smaller tumours a month later compared with controls.

Animals that had their tumours removed and then received the therapy, mimicking the surgical resection that a human would receive, had residual tumours 3.5 times smaller than controls two weeks later.

This shows, albeit in animal models of human disease, that cancer-homing stem cells can be safely prepared from human skin cells. These results, say the scientists, have a broad impact because NSC therapy is being explored for a range of metastatic, paediatric and peripheral cancer therapies...

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