Researchers at Weill Cornell Medicine, Cedars-Sinai Medical Center, and Roswell Park Comprehensive Cancer Center have developed genetically engineered CAR T cells that specifically target and kill bladder cancer cells, according to a June 26 announcement. The study, published in the Journal of Experimental Medicine, demonstrates that direct delivery of these CAR T cells via a catheter can control bladder tumors in mice.
Approximately 600,000 new cases of bladder cancer are diagnosed worldwide each year, including about 80,000 cases in the United States alone. Treatment typically involves surgical removal of the tumor followed by chemotherapy or immunotherapy. However, these approaches are associated with high recurrence and progression rates and often require complete removal of the bladder.
"For patients facing high-risk bladder cancer, options have historically been limited, highly morbid and life-altering. This reality has driven a critical, renewed interest in developing effective bladder-sparing approaches," said Parwiz Abrahimi, first author of the study conducted at Weill Cornell Medicine and currently a urologic oncologist at Cedars-Sinai Medical Center. The study was co-led by Professors Taha Merghoub and Jedd Wolchok from Weill Cornell Medicine and Professor Renier J. Brentjens from Roswell Park Comprehensive Cancer Center.
CAR T cells—immune cells genetically engineered to express an artificial receptor protein capable of targeting cancer cells—have been used successfully to treat various blood cancers but have shown limited success against solid tumors due to challenges such as poor tumor infiltration and off-target toxicity. To address this issue for bladder cancer treatment, researchers created CAR T cells with high specificity for a protein called MUC16 found on many types of bladder cancer cells but largely absent from normal tissues.
In laboratory tests using patient-derived tumors grown in the lab as well as human bladder cancer implanted into mice bladders, these MUC16-targeting CAR T cells were able to kill tumor cells effectively when delivered directly into the bladder via catheter (intravesical delivery). The approach reduced tumor growth and extended survival without spreading into other parts of the body or causing side effects elsewhere.
"Our findings establish MUC16 as a clinically relevant target for CAR T cell therapy in bladder cancer, and highlight that intravesical delivery... represents a feasible, effective, and readily easy-to-implement strategy for adoptive CAR T cell transfer," said Merghoub. "This approach could be useful for both initial treatment... as well as treatment refractory subsets... offering an attractive therapeutic option for patients who may have limited therapeutic alternatives besides bladder removal."
