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. The study, to be published June 26 in the Journal of Experimental Medicine ( JEM ), demonstrates that direct delivery of these CAR T cells via a catheter can control bladder tumors in mice, raising hopes that a similar approach may be effective in humans.
Approximately 600,000 new cases of bladder cancer are diagnosed worldwide each year, including about 80,000 cases in the US alone . Treatment generally involves surgical removal of the tumor followed by chemotherapy or immunotherapy. But these approaches are associated with high recurrence and progression rates, often necessitating 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 driven a critical, renewed interest in developing effective bladder-sparing approaches,” says Parwiz Abrahimi, first author of the study, which was carried out at Weill Cornell Medicine in New York, and currently a urologic oncologist at Cedars-Sinai Medical Center in Los Angeles, California. The new JEM study was co-led by Professors Taha Merghoub and Jedd 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 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.
When administered directly into the bladder, CAR T cells were unable to spread into the rest of the body, minimizing the risk of any side effects in other tissues.
“Development of engineered T cells for solid tumors has been challenging, in part due to normal tissue expression of potential target antigens,” Wolchok says. “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.”
Abrahimi et al., 2026. J. Exp. Med. https://rupress.org/jem/article-lookup/doi/10.1084/jem.20250699?PR
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Journal of Experimental Medicine ( JEM ) publishes peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions on research manuscripts are made through collaborative consultation between professional scientific editors and the academic editorial board. Established in 1896, JEM is published by Rockefeller University Press, a department of The Rockefeller University in New York. For more information, visit jem.org .
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Journal of Experimental Medicine
Experimental study
Animals
Intravesical mesothelin-based CAR T cells targeting MUC16 effectively control bladder cancer in preclinical models
26-Jun-2026
P. Abrahimi reported personal fees from Ferring Pharmaceuticals outside the submitted work; in addition, P. Abrahimi had a patent number 20240189426 pending. J.F. Khan reported a patent to antigen-recognizing receptors targeting B7- H3 pending. N. Chen reported a patent to chimeric receptors targeting MUC16 and uses thereof pending. M. Hamieh reported a patent to CAR T cell field licensed. B. Faltas reported grants from Eli Lilly, personal fees from UroToday, other from Guardant, and grants from Caris outside the submitted work. T.M. Carroll reported personal fees from Numen, nonfinancial support from Numen, and other from Numen during the conduct of the study; in addition, T.M. Carroll had a patent to Numen, related to methods of biomarker detection, pending. M.L. Everitt reported personal fees from Numen, nonfinancial support from Numen, and other from Numen during the conduct of the study. H.K. Subramanian reported personal fees from Numen during the conduct of the study and other from Numen outside the submitted work; in addition, H.K. Subramanian had a patent to Numen, related to methods of biomarker detection pending. H.A. Al-Ahmadie reported personal fees from AstraZeneca, Novartis, Janssen, and Pfizer outside the submitted work. O. Elemento reported personal fees from Volastra Therapeutics, other from Owkin and Harmonic, and grants from Eli Lilly outside the submitted work. R. Brentjens reported grants from BMS and personal fees from Atara Biotherapeutics, Triumvira, Cargo Tx, Legend Bio, Gracell Biotechnologies, and CoImmune outside the submitted work; in addition, R. Brentjens had patents to BMS, Caribou, and Sanofi with royalties paid. J.D. Wolchok reported grants from Bristol Myers Squibb during the conduct of the study; personal fees from Bristol Myers Squibb, Ascentage Pharma, Ankyra Therapeutics, Arsenal Biosciences, Imvaq Therapeutics, Tizona Therapeutics, Immunocore (Data Safety Board), Scancell, Apricity, XenImmune, Georgiamune, Linnaeus, and CellCarta outside the submitted work; in addition, J.D. Wolchok had a patent to xenogeneic DNA vaccines licensed (Merial), a patent to Newcastle disease viruses for cancer therapy licensed (Merck), a patent to myeloid-derived suppressor cell assay licensed (Caprion), a patent to anti-PD1 antibody licensed (Agenus), a patent to anti-CTLA4 antibodies licensed (Agenus), a patent to anti-GITR antibodies and methods of use thereof licensed (Agenus/Incyte), a patent to prediction of responsiveness to treatment with immunomodulatory therapeutics and method of monitoring abscopal effects during such treatment licensed (CellCarta), and a patent to antigen- recognizing receptors targeting B7-H3 and uses thereof pending. T. Merghoub reported a patent to WO2023034781A1; US20240189426A1 issued (NA), and acted in the capacity of consultant for ImmunOs Therapeutics, Daiichi Sankyo Co, TigaTx, Normunity, Pfizer, and LIfT BioSciences. T. Merghoub is a cofounder of and equity holder in IMVAQ Therapeutics and has received research support from Surface Oncology, Kyn Therapeutics, Infinity Pharmaceuticals, Peregrine Pharmaceuticals, Adaptive Biotechnologies, Leap Therapeutics, Aprea Therapeutics, Enterome SA, ReAlta Life Sciences, and Bristol Myers Squibb. T. Merghoub is also an inventor on patent applications related to work on oncolytic viral therapy, alpha virus–based vaccine, neoantigen modeling, immunomodulatory nanoparticles, bispecific activators, FLT3L, CD40, GITR, OX40, PD-1, CTLA-4, and chimeric receptors targeting melanoma differentiation antigens and B7-H3, and is listed as an inventor on a Provisional Patent Application related to work on CD47 and TSP- 1. No other disclosures were reported.