Stem cells target drugs at tumours
to become part of the supporting tissue. They can then act as
vehicles for drugs that are pumped into the cancer, sparing normal
tissue.
The discovery is set to cause ripples in cancer research, as the technique is the first viable approach to take advantage of a tumour's ability to attract these stem cells.
Tumours could be seen as 'never-healing wounds' that signal stem cells, using them to help build up "stromal," or connective tissue, that structurally supports and nurtures tumour growth. It has been shown that tumours constantly remodel their architecture with the help of these special stem cells, explaining the difficulty in administering drugs that are also effective.
The new approach uses human mesenchymal stem cells (MSC), the body's natural tissue regenerators. Tissue that is injured sends signals to these unspecialized, progenitor cells, and they, in turn, migrate to the damage and morph into whatever kind of tissue including bone, fat, muscle, cartilage, tendons, is needed to repair the wound.
Researchers at the University of Texas lead by Michael Andreeff, professor in the department of blood and marrow transplantation, isolated a small quantity of MSC from bone marrow, and then greatly expanded those cells in the lab. When the engineered mesenchymal progenitor cells engrafted where the tumour environment was signalling them, they activated the therapeutic gene.
In this study, they looked at whether MSC engineered to carry interferon beta could treat mice that were implanted with human breast cancer or human melanoma.
Andreef explained: "Interferon beta can inhibit cancer growth in laboratory tests, but is excessively toxic and short-lived when used at high doses as a therapy in patients."
"The team tested whether MSC engineered to express an interferon beta gene could provide a sustained and targeted effect directly to cancer cells."
For each of the two cancer types, the researchers tested three groups of mice against each other: one was an untreated control group, another was injected with interferon beta daily under the skin for three weeks, and the third received three weekly doses of intravenous MSC engineered to express the interferon beta payload.
The researchers found the MSC cellular vehicles grafted themselves into the tumour stroma and multiplied in number.The cells also delivered its drug over a long period of time, significantly improving survival of the mice. Specifically, mice whose breast cancer was treated with MSC survived 60 days compared to 41 days in the mice injected with interferon beta, and 37 days in untreated mice.
Mice with melanoma that were treated with MSC more than doubled their survival (73.5 days) compared with treated mice (32 days) and untreated mice (30 days).
The significance of this discovery proved that the cells were homing in on the tumours, delivering the anticancer treatment and opening up the possibility of testing a number of different payloads to see which is effective.
The approach could, in theory, be most effective for patients treated with radiation or chemotherapy because these therapies damage cancer cells, which would then be in critical need of MSC.
Andreef said that this homing strategy could offer a novel way to treat cancer that has spread.
"This drug delivery system is attracted to cancer cells no matter what form they are in or where they are," he commented.
