Lab-grown killer cells could treat brain tumours

"Scientists … have discovered a way of turning stem cells into killing machines to fight brain cancer," BBC News reports. While the results of this study were encouraging, the research involved mice, not humans.

The headline is prompted by the creation of stem cells genetically engineered to produce a type of poison known as pseudomonas exotoxin. This poison was made to target a specific type of brain tumour cell (glioblastoma) by linking it to antibody fragments.

This technique has been used with great success to treat blood cancers such as leukaemia, but has been less successful at treating solid tumours. The researchers suggest this is because it only remains active for a short amount of time (has a short half-life) and because it may be difficult to reach the tumour.

To overcome these problems, the researchers genetically engineered neural stem cells, which could make pseudomonas exotoxin while being resistant to the poison themselves.

The poison-making stem cells were able to kill these brain cancer cells both in the laboratory and in mice engineered to develop brain tumours.

The results are promising, but, as the researchers themselves point out, "Translation into human patients would need to be adapted to tackle the challenges imposed by the new host [a human being]".

Where did the story come from?

The study was carried out by researchers from Massachusetts General Hospital, the Dana-Farber Cancer Institute, and Harvard University.

It was funded by the US National Institutes of Health.

The study was published in the peer-reviewed biological journal, Stem Cells.

The story was well covered by BBC News and The Independent. Both make it clear this was a mouse study.

What kind of research was this?

This mouse study aimed to develop and test genetically engineered neural stem cells, which can make the poison pseudomonas exotoxin while being resistant to the poison themselves.

Pseudomonas exotoxin blocks cells from making proteins, which leads to the death of the targeted cells. The pseudomonas exotoxin was linked to an antibody fragment to target it at cells that had specific receptors present on their surfaces. These particular receptors are often present in glioblastomas (a specific type of brain tumour) and not on normal cells.

The researchers say pseudomonas exotoxin linked to antibody fragments have been used with great success to treat blood cancers, but have been less successful at treating solid tumours. They suggest this is because it only remains active for a short amount of time and it may be difficult to reach the tumour.

To overcome these problems, the researchers genetically engineered neural stem cells. So far the technique has only been tested in mice and on these specific cancer cells in the laboratory, so much more work will need to be done to ensure it is safe and effective in people.

What did the research involve?

Briefly, the researchers genetically engineered neural stem cells to make the poison pseudomonas exotoxin.

The researchers tested the activity of the poison-making stem cells on cells grown in the laboratory and on mice.

What were the basic results?

The researchers initially tested their poison-making stem cells on glioblastoma cells grown in the laboratory. When the stem cells and the glioblastoma cells were grown together, the glioblastoma cells died. The glioblastoma cells expressing the highest amount of the tumour-specific receptor were most sensitive to the stem cells.

The researchers then looked at whether the poison-making stem cells would work in animals. They mixed tumour cells and the poison-making stem cells and put them under the skin of mice. The poison-making stem cells were able to kill the tumour cells.

According to the researchers, one of the major limitations of current glioblastoma therapy is the inadequate distribution of chemotherapy drugs to the tumour that remains after surgery.

Surgery aims to remove all of the tumour, but cannot always remove all of it safely. Some tumours develop deep inside the brain, so removing them completely could lead to significant brain damage.

After surgery to remove a tumour, the researchers inserted poison-making stem cells in mice that were engineered to develop glioblastomas.

No tumours could be detected in mice who had the poison-making stem cells inserted by 21 days after surgery, but tumour masses could be detected in the control mice.

The poison-making stem cells also improved average survival from 26 days in the control group to 79 days in the treated mice.

The researchers finally tested the poison-making stem cells on glioblastoma cells from human patients. The poison-making stem cells were able to kill the glioblastoma cells that expressed the tumour-specific receptor.

How did the researchers interpret the results?

The researchers concluded that stem cell-based delivery of pseudomonas exotoxin can increase the likelihood of anti-tumour response by increasing the amount of time the poison is delivered for, and by eliminating the need for multiple invasive administrations.

Conclusion

This study has described the creation of genetically engineered neural stem cells that make the poison pseudomonas exotoxin. The stem cells were also made resistant to the poison themselves. The poison was linked to an antibody fragment to target it towards a specific type of brain tumour cell (glioblastoma).

Glioblastoma are usually very aggressive cancers, and the current treatment would usually involve surgical removal followed by radiotherapy and chemotherapy to try to kill the residual cancer cells.

This treatment regime can result in significant side effects, and there is no guarantee of achieving a complete cure.

In this study, the poison-making stem cells were able to kill these brain tumour cells both in the laboratory and in a mouse model.

So far the technique has only been tested in mice and on these specific brain cancer cells in the laboratory. This means much more work is needed to ensure it is safe and effective in people with brain cancer.

Glioblastomas also only account for a portion of all brain cancers. It is not known whether the treatment could ever be developed to treat other types of brain cancer.