New Research to Explore 'On and Off' Switch for CAR T-Cell Therapy

Nanoparticles that act as an ‘on and off’ switch could help improve the safety and efficacy of CAR T-cell therapy.

Researchers are working on an “on and off” switch to improve the safety and efficacy of chimeric antigen receptor (CAR) T-cell therapy and counter the treatment’s potential negative effects, according to a Notre Dame press release.

CAR T-cell therapy, which has been hailed as the “fifth pillar” of cancer treatment, is a novel treatment method that involves genetically engineering T-cells to target and kill cancer. However, serious missteps can occur with CAR T-cell therapy, including an off-target effect in which CAR T-cells attack off-target sites while completing their job.

To improve the safety and efficacy of this therapy, Notre Dame researchers are focusing on the use of nanoparticle-enabled technologies for CAR T-cell therapy in breast cancer. However, it has the potential to be applicable to other cancers that cause solid tumors to form as well.

According to the press release, the research team will create nanoparticles that act as an “on and off” switch to better control the risks of using traditional CAR T-cell therapy.

To do this, the researchers will develop a double-sided nanoparticle designed for 1 part to bind to the surface of a tumor while the other part can capture and activate the CAR T-cells. This nanoparticle will serve as a biomarker for CAR T-cells to identify the cancerous tumor but will dissipate from the tumor surface after a period of time, acting as an “off” switch for the modified CAR T-cells.

Additionally, the researchers plan to further improve the way CAR T-cell therapy is administered by using universal CAR T- (uCAR T) cells, which will make the process more efficient. When CAR T-cells are removed from a specific patient, it can take approximately 30 days to complete before administering treatment. Because uCAR T-cells are not derived from individual patients, they will be more readily available.

“Besides the safety risks of using the typical CAR T-cell therapy, it is also time consuming to develop and there is little control over the speed at which CAR T-cells kill a tumor,” Prakash D. Nallathamby, PhD, research assistant professor of aerospace and mechanical engineering, said in a press release. “Through this research, our goal is to address each of these concerns by using uCAR-T cells in combination with our proprietary modular double-sided nanoparticles to create a more manageable process for those giving and receiving the treatment.”

Reference

Developing an ‘On and Off’ Switch for Breast Cancer Treatment [news release]. Notre Dame’s website. https://research.nd.edu/news/developing-an-on-and-off-switch-for-breast-cancer-treatment/. Accessed August 20, 2018.