Armored CAR T Cells Break Through Immune Suppression in Solid Tumors

Researchers determined the safety and antitumor ability of genetically engineered CAR T cells that circumvent immune suppression in a prostate cancer phase I clinical trial.

Excerpt from the Press Release:

When developing chimeric antigen receptor (CAR) T cell therapy, researchers take T cells from a patient’s blood and engineer them to target specific antigens presented on cancer cells. These cutting-edge therapies have successfully fought blood cancers, killing the cells that they target. However, they are less effective at treating solid tumors due to the solid tumor microenvironment (TME), which suppresses the body’s immune system.

In a recent study published in Nature Medicine, Joseph Fraietta, a professor at the University of Pennsylvania, and his colleagues found a way to “armor” CAR T cells, giving them the ability to get past the immunosuppressive TME found in lethal metastatic castration-resistant prostate cancer.¹ “I’ve always wanted to do something aggressively translational,” said Fraietta. “It’s always about how do we move into human trials to make a therapy that’s really going to help cancer patients?”

One of the hallmarks of the immunosuppressive microenvironment is the inhibitory factor Tgfß1, which paralyzes the function of existing and engineered T cells. Fraietta and his colleagues wanted to prevent these CAR T cells from being poisoned by Tgfß once they get into the tumor microenvironment.

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