The genetic switch

Scientists have found an effective way to fight particularly dangerous cancer

Nadezhda Kovtan, Realist

Bioengineers at the University of California, San Diego have developed a control system that can make CAR-T-cell therapy safer and more effective in the treatment of cancer. By programming the activation of CAR-T cells when exposed to blue light, the researchers controlled the cells to destroy skin tumors in mice without harming healthy tissue.

This is reported in the journal Science Advances (Huang et al., Engineering light-controllable CAR T cells for cancer immunotherapy).

In tests on mice, the introduction of engineered CAR-T cells and stimulation of skin tumor sites with blue LED light reduced the tumor size by eight to nine times. The results were observed in nine out of ten mice tested. CAR-T cells by themselves did not inhibit tumor growth.

Chimeric antigen receptor (CAR) T-cell therapy represents a promising new approach to cancer treatment. It involves collecting the patient's T cells and genetically engineering them to express on their surface special receptors that can recognize the antigen on target cancer cells. The engineered T cells are then injected back into the patient's body to find and attack the cells on the surface of which the target antigen is located.

Despite the fact that this approach works well with some types of blood cancer and lymphoma, it still does not work well with solid tumors. One of the reasons is that many target antigens can also be found on healthy cells.

"It is very difficult to determine the ideal antigen for whole tumors with high specificity, so that CAR-T cells act only on these affected areas of the tumor, without harming normal organs and tissues. Thus, there is an urgent need to develop CAR-T cells that can be controlled with high precision in space and time," said Peter Yingxiao Wang, professor of bioengineering at the Jacobs School of Engineering at the University of California, author of the study.

To create such cells, Wang and his team installed a genetic switch that allowed them to activate CAR T cells at a specific location in the body. The implanted genes encode two proteins, which, with light pulses lasting one second, bind to each other and thereby trigger the synthesis of an antigen-targeted receptor.

Since light cannot penetrate deeply into the body, Wang suggests that this approach can be used to treat dense tumors near the surface of the skin. For future research, Wang is looking for opportunities to collaborate with doctors to test the approach on patients with melanoma.

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