A newly engineered T cell therapy has been developed that incorporates checkpoint inhibitor antibodies to provide the T cell with “armor” in order to evade the immunosuppressive tumor microenvironment and successfully fight solid tumors. Engineered T cell therapies such as chimeric antigen receptor (CAR) T cells have been shown to be effective in blood cancers like lymphoma and leukemia, however, the approach hasn’t been successful in treating solid tumors. The proof-of-concept study was the result of a collaboration between Eureka Therapeutics and Memorial Sloan Kettering Cancer Center (MSKCC) and the results were published today in Nature Biotechnology.
Checkpoint inhibitors are monoclonal antibodies that target proteins, such as PD-1, that are used by cancer cells to hide from the immune system. These inhibitors have been successful at treating solid tumors. The engineered CAR-T cells in this study were designed to produce a single-variable fragment (scFv) PD-1 blocking antibody that is similar to commercially available checkpoint inhibitor drugs. The antibody blocks PD-1 which provides the CAR T cells and other neighboring immune cells with time to kill the cancer cells.
The research team tested two types of the novel armored CAR-T cells—one that targeted B-cell cancers and another that targeted ovarian and pancreatic cancer—in vivo using mouse models. The study findings were two-fold. They showed that CAR-T cells expressing a PD-1 antibody were able to stay near the tumor site longer suggesting that they avoided the toxicity associated with traditional checkpoint inhibitors. Also, enabling the PD-1 antibodies to go directly inside the tumor signaled other neighboring tumor fighting T cells to step up and join the fight.
The hope is that this new CAR-T cell will be the foundation for other targeted therapies. “We can build CAR-T cells to secrete a variety of different molecules, tailored to the needs of the patient,” he says. “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.