Catheter-Delivered CAR-T Cells Target Bladder Cancer in New Bladder-Sparing Approach

Researchers at Weill Cornell Medicine, Cedars-Sinai Medical Center, and Roswell Park Comprehensive Cancer Center have engineered specialized CAR-T cells capable of specifically targeting and destroying bladder cancer cells. Published in the Journal of Experimental Medicine (JEM), the study demonstrates that delivering these CAR-T cells directly into the bladder via a catheter effectively controls bladder tumors in mice, raising hopes for a similar therapeutic approach in human clinical settings.

Globally, approximately 600,000 new cases of bladder cancer are diagnosed each year, with around 80,000 occurring in the United States alone. Standard treatment typically involves surgical tumor resection followed by chemotherapy or immunotherapy. However, these conventional approaches carry high rates of recurrence and disease progression, often necessitating radical cystectomy—a life-altering surgery that completely removes the bladder and can lead to severe postoperative complications.

"For patients with high-risk bladder cancer, treatment options have historically been limited, morbid, and life-changing. This reality motivated us to refocus on developing effective bladder-sparing therapeutic strategies," says lead author Dr. Parwiz Abrahimi, who completed the research at Weill Cornell Medicine in New York and is now a urologic oncologist at Cedars-Sinai Medical Center in Los Angeles.

The new JEM study was co-led by Dr. Taha Merghoub and Dr. Jedd Wolchok at Weill Cornell Medicine, alongside Dr. Renier J. Brentjens at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

Targeting a Specific Bladder Cancer Biomarker

CAR-T cells—immune cells genetically engineered to express artificial chimeric antigen receptors that specifically target cancer cells—have achieved remarkable success in treating various hematologic malignancies. However, their efficacy against solid tumors has been limited to date by hurdles such as poor tumor infiltration and off-target toxicities.

Dr. Abrahimi’s team sought to overcome these obstacles by generating CAR-T cells with high specificity for bladder cancer cells and delivering them directly into the bladder via a catheter (intravesical instillation).

Figure 1. Comprehensive transcriptomics-based analysis identifies MUC16 as a potential target for CAR T cell therapy of BCa. (Abrahimi P, et al., 2026)

The researchers engineered CAR-T cells that recognize a protein called MUC16. This protein is highly expressed on the surface of many bladder cancer cells—including subtypes resistant to existing therapies—while being virtually absent in normal bladder tissue and other healthy organs. In laboratory settings, these engineered CAR-T cells successfully eliminated MUC16-positive tumors grown from patient-derived bladder cancer cells.

Direct Regional Delivery Holds the Key

The team subsequently tested the capacity of these CAR-T cells to control the growth of human bladder cancer cells implanted in mouse bladders. When administered intravenously, the CAR-T cells showed no therapeutic efficacy. However, when delivered intravesically directly into the bladder, they significantly blunted tumor growth and extended overall survival.

By injecting the CAR-T cells directly into the bladder, the engineered cells were prevented from disseminating to other parts of the body, thereby minimizing the risk of systemic side effects in off-target tissues.

"Developing engineered T-cell therapies for solid tumors has been challenging, partly because many potential target antigens are also expressed on healthy tissues," says Dr. Wolchok. "Utilizing a regional delivery system allows us to overcome this barrier, bringing us one step closer to broader applications of CAR and TCR-engineered T-cell therapies in common solid tumors like bladder cancer."

A Novel Pathway to Bladder Preservation

"Our study establishes MUC16 as a clinically relevant target for CAR-T cell therapy in bladder cancer and highlights that intravesical instillation—a routinely used administration route in urological practice—is a feasible, effective, and readily implementable strategy for adoptive CAR-T cell transfer," says Dr. Merghoub.

"This strategy could serve as an initial treatment for bladder cancer as well as an intervention for refractory tumor subtypes, offering an attractive therapeutic alternative for patients who otherwise have limited options beyond radical cystectomy."