Eureka Therapeutics and Memorial Sloan Kettering (MSK) have built a new model of CAR-T cells, ones with powerful “armor” that allow them to fight solid tumors. A paper describing the approach was published in the journal Nature Biotechnology.

The new cells combine two of the most promising types of immunotherapy – chimeric antigen receptor (CAR) T cells and checkpoint inhibitors – into one package. By engineering checkpoint inhibitors directly into the CAR-T cell itself, scientists believe they can limit the side effects of these drugs while taking advantage of their powerful immune-stimulating capabilities.

The newly designed CAR-T cells secrete a mini version of a checkpoint-blocking antibody similar to the drugs nivolumab (Opdivo) and pembrolizumab (Keytruda), which are approved for the treatment of several types of cancer. The antibody binds to a protein called PD-1 that acts like a brake on immune cells. The antibody releases this brake, allowing the CAR T cells and surrounding immune cells to better fight the disease.

In all cases, including mouse models of solid tumors, the team found that the armored CARs persisted longer in the body than standard CARs and they produced better results-the mice lived longer

In addition, because the checkpoint drugs were released directly into the tumor, they activated nearby T cells, creating a helpful bystander effect. The companies say the approach can be thought of as providing a new platform for CAR therapy.

“We can build CAR-T cells to secrete a variety of different molecules, tailored to the needs of the patient. It’s not just limited to this one drug,” said Renier Brentjens, director of the Cellular Therapeutics Center at MSK and one of the pioneers of CAR therapy.