Researchers at Weill Cornell Medicine, Cedars-Sinai Medical Center, and Roswell Park Comprehensive Cancer Center have developed engineered CAR T cells that specifically target and kill bladder cancer cells. This study was published on June 26th. experimental medicine journal (gem) have demonstrated that direct delivery of these CAR T cells via catheter can control bladder tumors in mice, raising hopes that a similar approach may be effective in humans.
Each year, approximately 600,000 people are newly diagnosed with bladder cancer worldwide, including approximately 80,000 in the United States alone. Treatment usually 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, a life-altering procedure that can lead to significant complications.
“For patients facing high-risk bladder cancer, options have historically been limited, highly morbid, and life-altering. This reality has sparked significant renewed interest in developing effective bladder-sparing approaches,” says Parwiz Abrahimi, lead author of the study conducted at Weill Cornell Medicine in New York and now a urological oncologist at Cedars-Sinai Medical Center in Los Angeles, California. new gem The study was co-led by Professors Taha Melghoub and Jed Wolchok of Weill Cornell Medicine and Professor Renier J. Brentjens of Roswell Park Comprehensive Cancer Center in Buffalo, New York.
CAR T cells (immune cells genetically engineered to express artificial receptor proteins that can specifically target cancer cells) have been successfully used to treat many different types of blood cancers. However, their success against solid tumors has so far been limited due to challenges such as poor tumor invasion and off-target toxicity. Abrahimi et al. attempted to overcome these problems by creating CAR T cells with high specificity for bladder cancer cells and delivering them directly to the bladder via a catheter (also called 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 treatments, but is largely absent from normal bladder cells and other healthy tissues. These CAR T cells were able to kill MUC16-positive tumors grown from patient-derived bladder cancer cells in the lab.
Abrahimi et al. They then tested the ability of these CAR T cells to control the growth of human bladder cancer cells transplanted into the bladders of mice. CAR T cells had no effect when administered intravenously. However, intravesical delivery of the cells reduced tumor growth and prolonged survival.
When administered directly into the bladder, CAR T cells were unable to spread to other parts of the body, minimizing the risk of side effects in other tissues.
The development of engineered T cells for solid tumors has been difficult, due in part to normal tissue expression of potential target antigens. By using a compartmentalized delivery system, we hope to overcome this hurdle and move one step closer to widespread use of CARs and transgenic T cells for common solid tumors such as bladder cancer. ”
Jed Wolchok, Weill Cornell Medicine
“Our findings establish MUC16 as a clinically relevant target for CAR T-cell therapy in bladder cancer and highlight that intravesical delivery, a route of administration commonly used in urological practice, is a feasible, effective, and easily implemented strategy for adoptive CAR T-cell transfer,” says Merghoub. “This approach may be useful both in the initial treatment of bladder cancer as well as in treatment-resistant tumor subsets, providing an attractive treatment option for patients for whom treatment options other than cystectomy are limited.”
sauce:
Rockefeller University Press
Reference magazines:
Abraham, P. others. (2026). Intravesical mesothelin-based CAR T cells targeting MUC16 effectively control bladder cancer in preclinical models. Journal of Experimental Medicine. DOI: 10.1084/jem.20250699. https://rupress.org/jem/article/223/7/e20250699/282767/Intravesical-mesothelin-based-CAR-T-cells
