This ‘genetic switch’ could help to fight cancer


Scientists have devised a remote-control method that could one day be used to make the immune system mount a powerful anti-cancer attack inside tumors.

Researchers want to use the new method to help immune cells to defeat cancer cells.

The technique was developed at the Georgia Institute of Technology (Georgia Tech) in Atlanta and uses engineered genes, laser technology, and gold nanoparticles to get T cells inserted into tumors to vastly increase production of specific proteins.

T cells are a type of white blood cell that have an inbuilt ability to detect and kill cancer cells, which, unfortunately, some tumors can switch off.

However, the team’s new method offers a way to switch anti-cancer ability in T cells back on again.

A paper that is now published in the journal ACS Synthetic Biology describes how the approach triggered “gene expression at specific sites to levels greater than 200-fold” inside tumors implanted in mice.

The team now plans to develop the method to increase production of proteins that help immune cells to target and kill cancer cells. They hope that one day it will serve as a “precision tool” for fighting cancer.

“In upcoming experiments,” says principal investigator Gabriel A. Kwong, an assistant professor of biomedical engineering at Georgia Tech, “we are implementing this approach to treat aggressive tumors and establish cancer-fighting effectiveness.”

A type of immunotherapy

The technique is a type of immunotherapy, which is a relatively new way of treating disease by boosting or adapting defense mechanisms that are naturally present in the body.
There are several types of immunotherapy for cancer, and they each work in a different way.

Some stop or slow the growth of tumor cells, while others stop cancer spreading to new sites, or metastasizing. And some, such as the one that Prof. Kwong and colleagues are working on, help the immune system to kill cancer cells.

An example of immunotherapy that hit the headlines was the successful treatment in 2015 of former United States president Jimmy Carter, when he was aged 91.

Doctors treated his metastatic melanoma — which had spread to his liver and his brain — with a combination of radiation and immunotherapy. Three months later, the secondary tumors had disappeared.

Heat-activated ‘genetic switch’

In their study paper, Prof. Kwong and his team describe how they inserted a “genetic switch” inside T cells that is activated when it reaches a particular temperature.
When this switch is turned on, it can make the T cell vastly increase its production of specific proteins.
The researchers introduced the T cells, with their genetic switches turned off, into tumors that had been implanted into mice. They had seeded the tumors beforehand with gold nanoparticles.

They then shone a near-infrared laser onto the tumors from outside the mice’s bodies. This made the gold nanoparticles generate heat and warm up the tumors and the T cells inside them.

When the temperature reached 40–45°C (104–113°F), it turned on the engineered genetic switches in the T cells and greatly increased gene expression that controls the production of specific proteins.

The researchers point out that, similar to many other T cell therapies, theirs is very new and has a long way to go before it is ready to treat cancer.

This study is a step toward making it even more effective.”
Prof. Gabriel A. Kwong



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