Engineered CAR T cells successfully target bladder cancer in mice
· News-MedicalCAR T cells-immune cells genetically engineered to express an artificial receptor protein capable of specifically targeting cancer cells-have been successfully used to treat many different types of blood cancer. But their success against solid tumors has so far been limited due to challenges including poor tumor infiltration and off-target toxicity. Abrahimi et al. attempted to overcome these issues by creating CAR T cells with high specificity for bladder cancer cells and then delivering them directly to the bladder via a catheter (also known as intravesical delivery).
The researchers generated CAR T cells that recognize a protein called MUC16. This protein is highly expressed on the surface of many bladder cancer cells, including types that are resistant to existing therapies, but is largely absent from normal bladder cells and other healthy tissues. These CAR T cells were able to kill MUC16-positive tumors grown in the lab from patient-derived bladder cancer cells.
Abrahimi et al. then tested the ability of these CAR T cells to control the growth of human bladder cancer cells implanted in the bladders of mice. The CAR T cells were ineffective when administered intravenously. When the cells were delivered intravesically, however, they reduced tumor growth and extended survival.
Jedd Wolchok, Weill Cornell MedicineDevelopment of engineered T cells for solid tumors has been challenging, in part due to normal tissue expression of potential target antigens. Using a compartmentalized delivery system allows us to overcome this hurdle and hopefully come one step closer to broader use of CAR and transgenic T cells for common solid tumors, like bladder cancer."
"Our findings establish MUC16 as a clinically relevant target for CAR T cell therapy in bladder cancer, and highlight that intravesical delivery, a commonly used administration route in urological practice, represents a feasible, effective, and readily easy-to-implement strategy for adoptive CAR T cell transfer," Merghoub says. "This approach could be useful for both initial treatment of bladder cancer as well as treatment refractory subsets of tumors, offering an attractive therapeutic option for patients who may have limited therapeutic alternatives besides bladder removal."
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