Stem cells that release cancer-killing toxins offer new brain tumor treatment

Date: Oct-27-2014 A new way to to use stem cells to fight brain cancer is revealed in

a proof-of-concept study published in the journal Stem Cells, where

scientists describe how they got the cells to produce and release toxins

that kill only tumor cells.

The researchers genetically engineered stem cells to make and secrete toxins that kill brain cancer cells without themselves being affected.

Led by Dr. Khalid Shah, a neuroscientist at Harvard Stem Cell Institute,

Harvard University, in Cambridge, MA, and also of Massachusetts General

Hospital (MGH) in Boston, MA, the scientists found the toxin-releasing stem

cells eliminated cancer cells left behind in mouse brains following tumor

removal.

In recently published work, Dr. Shah showed how stem cells loaded with herpes can kill brain

tumors. In this new study, he and his colleagues describe how they

genetically engineered stem cells to make and secrete toxins that kill brain

cancer cells without themselves being affected.

The toxins that the stem cells make are cytotoxins - they enter and kill

cells within days by stopping their ability to make proteins, which prevents

them growing, dividing and reproducing.

Cytotoxins are deadly to all cells, but in the late 1990s, scientists

found a way to tag them so they only entered cancer cells with certain

molecules on their surfaces. Normal cells without the surface molecules are

unharmed.

Dr. Shah, who directs the Molecular Neurotherapy and Imaging Lab at MGH

and Harvard Medical School, says:

"Cancer-killing toxins have been used with great success in a variety of

blood cancers, but they don't work as well in solid tumors because the

cancers aren't as accessible and the toxins have a short half-life."

He and his colleagues put the stem cells inside a capsule of

biodegradable gel that they deposited in the tumor site after removal. This

appeared to overcome the problems of approaches that have tried to deliver

purified cancer-killing toxins into patients' brains - methods that have not

succeeded in clinical trials.

The team is seeking federal approval for this and other stem cell

techniques they have developed so they can proceed to clinical trial.

Genetically engineered stem cells that are resistant to cytotoxin

Dr. Shah explains that, a few years ago, they saw how stem cells could be

used to provide a continuous supply of such therapeutic toxins to treat

brain tumors, but the problem was how to do it without the toxins killing

the stem cells themselves.

They eventually found a way to genetically engineer the stem cells so

they did not succumb to the toxins they produced:

"Now, we have toxin-resistant stem cells that can make and release

cancer-killing drugs," he adds.

To accomplish this, they engineered human neural stem cells with a

mutation that does not allow the toxin to act inside the cell. They also

inserted a piece of genetic code so the stem cells can make and release

tagged toxin that targets cancer cells.

When the toxin enters the target cancer cells, as they do not have the

protective mutation, they eventually stop working and die. Dr. Shah explains

how they tested this effect in mice:

"We tested these stem cells in a clinically relevant mouse model of brain

cancer, where you resect the tumors and then implant the stem cells

encapsulated in a gel into the resection cavity."

Prolonged survival in animals with surgically removed brain tumors

After doing all of the molecular analysis and imaging to track the

inhibition of protein synthesis within brain tumors," says Dr. Shah, "we do

see the toxins kill the cancer cells and eventually prolonging the survival

in animal models of resected brain tumors."

The team now plans to bring together the results of experiments with

toxin-releasing stem cells, and the different types of therapeutic stem

cells they have developed, to refine their method in mice with glioblastoma,

the most common brain tumor in human adults.

Dr. Shah expects to be starting clinical trials of the method within 5

years.

The study was funded by the National Institutes of Health and the James

S. McDonnell Foundation.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.