Dr Róisín Dwyer is using adult stem cells to seek out and target tumours. Claire O’Connell found out more about how she is developing ‘stealth vehicles’ to deliver anti-cancer treatment.
Tumours aren’t always the easiest things to find. They can be small, or tucked away in obscure places. If only something could travel around the body and track them down.
But wait … there is something. Adult stem cells have a particular talent for ‘finding’ tumours, explains Dr Róisín Dwyer, a lecturer in translational science at NUI Galway, who is looking to harness the cells as stealth vehicles.
Her approach is to take adult stem cells, give them a gene to carry and set them off like stealth delivery vehicles to find tumour sites. Then when the stem cells bring the gene to the tumour site, they can act as targets for a treatment that kills nearby cancer cells.
Stem cells heal – and find
So why adult stem cells? Mesenchymal stem cells occur naturally in bone marrow and their normal role is in wound healing and encouraging tissue to regenerate, explains Dwyer.
“If there is inflammation or the generation of a new scar then stem cells will travel from the bone marrow directly to the site of injury and generate new tissue and repair the wound,” she says. “Tumours are very like wounds and we think this is why these stem cells go to them.”
And one of the big advantages is that the stem cells seem to cruise around under the immune system’s radar, adds Dwyer. “The host immune system doesn’t seem to recognise them – I could donate my stem cells to you and there wouldn’t be any reaction.”
Delivering the goods
So if you can use a stem cell to find a tumour, what then? Dwyer’s approach is to engineer the stem cells so they are carrying an important gene for anti-cancer treatment – one that lets radioactive iodide get inside the stem cell.
That works well for a couple of reasons – first, the researchers can track the stem cells as they move around by giving tracer doses of radioactive iodide, allowing them to image where the cells are in organs and tissues. Then when they can see that the stem cells have concentrated at a tumour site they can give a higher dose of radioactive iodide that blitzes the cells at that spot.
“In our model we are killing off the stem cells when they arrive at the tumour site and thereby killing the surrounding tumour, as well,” explains Dwyer, who has collaborated on the project with the Regenerative Medicine Institute and Discipline of Physics at NUI Galway, the Center for Gamma Ray Imaging in Arizona, and the Mayo Clinic, which has locations across the US.
Fortune favours the patient
So far, the results in animal studies have shown positive results, but there was a point at which things took a frustrating turn. Initially, when the researchers introduced the genetically-loaded stem cells and tracked where they went, the cells seemed not to be finding their way that efficiently.
“We watched them as they travelled around, and after a couple of days there was some engraftment at the tumour site but still there were a lot of cells that weren’t at the site, which was disappointing,” she says.
But then they waited a little longer and breathed a sigh of relief as the results unfolded. “Two weeks later, the stem cells were really only at the tumour site and they had cleared from other tissues,” recalls Dwyer. “It brought back to us how important it is to be able to watch and image them as they move around.”
Once the ‘stealth vehicle’ stem cells were in place at the tumour sites, a higher dose of radioactive iodide resulted in the tumours shrinking, explains Dwyer, who received funding for the work through the Health Research Board and the Irish Cancer Society, and who won the Irish Cancer Society’s Researcher of the Year award in 2011.
Moving to the clinic
Now that the approach has been shown to work in the lab, Dwyer is looking closely at how the stem cells communicate with each other, and the longer-term effects of having the cells at a tumour site.
“It’s very promising in terms of getting it to clinical trials but what we have to do first is work out how the cells are talking to one another,” she explains. “We know the stem cells go there and we can use our therapy, but some stem cells may get left behind and we want to know what are they doing – we are interested in looking for any caveats, and we want to do longer-term studies, as well.”
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