On October 1, 2026 Roswell Park Comprehensive Cancer Center ("Roswell Park") and Generate Biomedicines, Inc. ("Generate") reported that the first patient has been dosed in a first-in-human clinical trial evaluating GB-5267, an investigational, autologous IL-18 armored CAR T-cell therapy designed to overcome key barriers that have limited the success of cellular therapies in ovarian cancer and other solid tumors. GB-5267 targets the antigen MUC16, which is over-expressed by more than 80% of ovarian tumors and helps them grow, spread, and hide from the immune system. The trial is recruiting patients whose disease has returned after treatment or does not respond to platinum-based chemotherapy, the standard first-line treatment.
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Led by Principal Investigator Emese Zsiros, MD, PhD, FACOG, Chair of Gynecologic Oncology at Roswell Park, the phase 1 clinical trial (NCT07489287) will evaluate the safety and tolerability of GB-5267.
Each patient’s T cells, immune cells capable of killing cancer cells, will be collected, genetically engineered, and expanded in Roswell Park’s GMP Engineering & Cell Manufacturing Facility before being returned to the patient to target an attack against the tumor.
While T-cell therapies have revolutionized the treatment of blood cancers, leading to long-term remission or even cure for many patients, solid tumors — cancers that grow in organs or tissue — have posed more of a challenge. That’s because the tumor’s microenvironment, a protective cocoon that surrounds it, prevents immune cells from entering the tumor or even being able to recognize it. But investigators believe they have found a way around that roadblock.
"We’re armoring the T cells with IL-18, a cytokine that will help protect them from the suppressive microenvironment of the solid tumor," explains Marco Davila, MD, PhD, Senior Vice President and Associate Director for Translational Research at Roswell Park. Dr. Davila co-developed some of the first CAR T-cell therapies and has played a key role in refining them.
"Because ovarian cancer spreads through the peritoneal cavity, the CAR T-cell therapy will be delivered in two ways: intravenously and into the peritoneal cavity," adds Dr. Zsiros. "This strategy is designed to concentrate the immune response where it is needed, without the toxicity of high-dose chemotherapy."
GB-5267 was engineered by Generate with AI through the design and evaluation of CAR architectures at scale based on how T cells actually behave, rather than relying on binding affinity as a proxy for performance. GB-5267 was designed to optimize three interdependent functions required for CAR T-cell performance in solid tumors:
Potency, the ability to kill MUC16-expressing tumor cells
Proliferation, the ability to expand into a larger T-cell population
Persistence, the ability to remain active over time in a suppressive tumor microenvironment
"Recognizing a tumor antigen is only one part of the challenge. In solid tumors, a CAR T cell that kills but does not expand or persist is a partial solution. GB-5267 was computationally designed with potency, proliferation, and persistence to maintain activity in a suppressive tumor microenvironment. Dosing the first patient begins the clinical test of whether that function-first approach behaves in patients as intended," says Dinesh de Alwis, PhD, Senior Vice President and Head of Clinical Drug Development at Generate Biomedicines.
Unlike many CAR T-cell approaches, this study will not require lymphodepletion, which uses chemotherapy to reduce the patient’s original immune cells to provide more space for the new cells. That means patients will not be exposed to the side effects associated with chemotherapy.
Typically, ovarian cancer is treated with surgery followed by platinum-based chemotherapy. When the disease recurs, it often no longer responds to chemotherapy, at which point it is very difficult to treat, with few options. The five-year relative survival rate for the disease is only 51.6%.
"CAR T-cell therapy has transformed outcomes in blood cancers," says Dr. Zsiros. "With this clinical trial, we are working to bring that progress to people with ovarian cancer."
Research leading to this clinical trial was made possible in part by donations to the Roswell Park Alliance Foundation’s Igniting Cancer Breakthroughs campaign and through events like Ride for Roswell.
(Press release, Generate Biomedicines, OCT 1, 2026, View Source;docid=6a8c470cfd9da29fbe47c53131417eea49df4ad9&content=prnews&format=html [SID1234671219])