Trying Nanoparticles, CAR T-Cell Therapy, and CRISPR to Treat Metastatic Cancers in Mice

Grantee: Matthias Stephan, MD, PhD
Institution: Fred Hutchinson Cancer Research Center
Focus Area: Leukemia, Immunology, and Blood Cell Development
Term: 7/1/2016 to 6/30/2020

The Challenge: CAR T-cell therapy requires re-engineering specific genes in a type of immune cell called T-cells. To create the treatment, a patient’s own T-cells are removed and sent to a lab, where they are changed by adding a man-made chimeric antigen receptor (CAR). Then those altered T-cells, with the added CAR, are injected back into the patient. The CAR helps the T-cells locate and destroy cancer cells.

The FDA has approved CAR T-cell drugs for certain blood cancers, but CAR T-cell drugs for solid tumors, like ovarian cancer, are only available in clinical trials. 

The Research: Matthias Stephan, MD, PhD, and his team are testing a new way to add a CAR to T-cells in mice with ovarian cancer. They’re using extremely tiny, atomic-size substances called nanoparticles to deliver genes to T-cells. That way, the re-engineering to add a CAR happens in the blood, not in a lab. The team hopes this technique may allow CAR-T treatment to start working faster than the current method.

Stephan and his team are also studying another type of programmed nanoparticle that they hope can identify different molecules on cancer cells.

In addition, the team is studying if nanoparticles can help deliver a genome editing system called CRISPR to stop the natural braking system of immune cells. They hope the nanoparticle-programmed T-cells show better results than the current method of CAR-T therapy.

The Goal and Long-Term Possibilities: In the future, the researchers hope doctors might be able to use a nanoparticle to treat cancer in certain people immediately, before the disease becomes advanced. 

*Funded by the HOPE Foundation