CAR-T Goes Hot: Laser Pulses-heated CAR-T Cells Show Better Efficiency

CAR T-cell therapy has been lauded as a feasible solution for several cancers by patients, clinical researchers, investors, and the media. As a fact, it is now one of the most intriguing research fields in life sciences, as well as a growing research field of immunotherapy, with over 500 clinical trials studying CAR T-cell therapies as possible cancer treatments. A group of researchers lead by scientists at the Georgia Institute of Technology claimed an improvement in the accuracy and capability of CAR T-cell therapy. The study, which was just published in Nature Biomedical Engineering, titled Enhanced intratumoral activity of CAR T cells engineered to produce immunomodulators under photothermal control, is changing the research on oncology.

In CAR T-cell treatment, a patient's T cells, a kind of white blood cell, are genetically modified in a laboratory. The patient's immune cells are then given a chimeric antigen receptor (CAR) and reintroduced to the body, where they target out and destroy cancer cells. That's how they work.

The senior study investigator Gabe Kwong, author of this paper, said that these therapies have proven to be effective for patients with liquid tumors, but for solid tumors, such as sarcomas, carcinomas, they don’t work well since CAR T-cells are immunosuppressed by the tumor microenvironment.

To improve the way CAR T-cells attack cancer, Kwong and his collaborators are altering the environment and introducing cell changes. They engineered T cells with a genetic on-off switch and created a remote-control system that sends the modified T cells on a precise invasion of the tumor microenvironment, where they destroy the tumor and prevent recurrence.

The new discovery expands on the lab's previous research into remotely controlled cell treatment strategy. Researchers can precisely target tumors using localized heat deposition, wherever they are in the body. The heat stimulates the CAR T-cells inside the tumors, thus overcoming immunosuppressive problems.

The researchers did not treat tumors clinically in the previous trial, but they are doing so now with the novel technology. They used laser pulses from outside the animal's body to produce heat in the tumor of a mouse. Gold nanorods transported to the tumor convert light waves into localized, medium heat, elevating the temperature to 40-42 °C, which is just hot enough to activate the T cells' on-switch without killing healthy tissue or T cells. The cells can boost the expression of cancer-fighting proteins once they are turned on.

"We showed that the activity of intratumoral CAR T-cells could be controlled photothermally via synthetic gene switches that trigger the expression of transgenes in response to mild temperature elevations," the authors wrote. "In vitro, heating engineered primary human T cells for 15-30?min led to over 60-fold-higher expression of a reporter transgene without affecting the cells’ proliferation, migration, and cytotoxicity. In mice, CAR T-cells photothermally heated via gold nanorods produced a transgene only within the tumors."

The method healed cancer in mice, according to the current research, and the team's strategy not only eliminated tumors but also prevented recurrence, which is significant for long-term survival. They will go further with the research by focusing on the further customization of T cells as well as how the heat is delivered to the tumor.