"Gene circuit switch" triggers immune attack on cancer cells

Source: Xinhua| 2017-10-20 03:26:39|Editor: Mu Xuequan
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WASHINGTON, Oct. 19 (Xinhua) -- U.S. researchers said Thursday they have developed a synthetic "gene circuit" that triggers the body's immune system to attack cancers when it detects signs of the disease.

The circuit will only activate a therapeutic response when it detects two specific cancer markers, according to Timothy Lu, associate professor of biological engineering and of electrical engineering and computer science at the Massachusetts Institute of Technology.

The approach, billed as an advance that may open new pathways for cancer immunotherapy and described in a paper in the journal Cell, has been demonstrated successfully in several recent clinical trials, Lu said.

Lu and his colleagues built the circuit encoded in DNA based on principles similar to the simple AND gates used in electronics, which will only switch on a circuit when two inputs are present.

Since cancer cells differ from normal cells in the profile of their gene expression, the researchers developed synthetic promoters -- DNA sequences designed to initiate gene expression but only in cancer cells.

When the circuit is delivered to cells in the affected area of the body using a virus, the synthetic promotors will bind to certain proteins that are active in tumor cells, causing the promoters to turn on.

"Only when two of these cancer promoters are activated, does the circuit itself switch on," Lu said.

This allows the circuit to target tumors more accurately than existing therapies, as it requires two cancer-specific signals to be present before it will respond, he said.

When the researchers tested the circuit in vitro, they found that it was able to detect ovarian cancer cells from amongst other noncancerous ovarian cells and other cell types.

They then tested the circuit in mice implanted with ovarian cancer cells, and demonstrated that it could trigger T cells to seek out and kill the cancer cells without harming other cells around them.

Finally, the researchers showed that the circuit could be readily converted to target other cancer cells, including those from breast cancer.

Ultimately, they hoped they will also be able to use the system to target other diseases, such as rheumatoid arthritis, inflammatory bowel disease, and other autoimmune diseases.

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