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Accelerating Immunotherapy
New lymphoma T-cell therapy, made in less than a day, shows promising results with fewer side effects
Photo by Matt ShifflerCase Comprehensive Cancer Center pathologist David Wald developed an experimental drug, and in results available so far, 13 of 15 patients with lymphomas went into complete remission after receiving it.Each of the patients was at a crossroads. Conventional chemotherapy for their lymphomas had failed—one, twice, half-a-dozen times.
Now, each had a choice: They could take a U.S. Food and Drug Administration (FDA)-approved immunotherapy drug that's effective about half of the time but also comes with serious risks. Or they could volunteer to be among the first to try an experimental drug developed by Case Comprehensive Cancer Center pathologist David Wald, PhD, MD (GRS '03, pathology; MED '05). Researchers suspected the drug, called UF-Kure19, might have fewer side effects, and they hoped that maybe, possibly, it could shift those 50-50 odds in the patients' favor.
Today, nearly two years after the first patient received UF-Kure19, 14 more have taken a chance on the new drug in Cleveland and Iowa City, Iowa. In results available so far, 13 patients went into complete remission while still exhibiting far fewer side effects than they might have had with similar drugs.
UF-Kure19 is part of a family of treatments called CAR-T cell therapies. These drugs transform patients' own immune cells into cancer killers. But unlike other CAR-T drugs, which take up to two weeks to produce, UF-Kure19 is made in less than a day, thanks to an innovative ultrafast manufacturing process pioneered by Wald, the John D. Crissman and Francis D. Drake Professor in Pathology at Case Western Reserve's School of Medicine and co-leader of the cancer center's Immune Oncology Program.
"CAR-T cell therapy is essentially a living drug," said Wald, also a pathologist with (UH). Typically, CAR-T cell therapy starts with drawing some of the patient's blood and separating out T cells, which are immune cells that can learn to identify and kill pathogens. Once isolated, the patient's T cells are genetically modified to spot and kill cancer cells, then grown in culture for a few weeks. Thus armed, they are then infused back into the patient's bloodstream, where they multiply and start attacking cancer.
More than 30,000 people, mostly patients with blood cancers for whom other therapies have failed, have been treated with CAR-T cell drugs since the first such drug was approved by the FDA in 2017. Some are cured. But the drugs don't work for everyone.
About half the patients relapse within a year, Wald said. Others get much sicker while waiting for their modified T cells to be ready. The drugs also can also cause serious side effects, including potentially fatal immune responses and neurological problems, and are extremely costly.
Wald believes UF-Kure19 could be lifesaving for thousands of patients with blood cancers like lymphoma who can't afford—and can't afford to wait for—traditional CAR-T cell therapy, or who live too far from a treatment center that offers it. In 2022, he co-founded a company, Kure.ai that he said is working closely with CWRU and UH, to further develop this technology so that cancer patients worldwide have access to safer, more effective and lower cost CAR-T therapies. He and his team are also applying the same technology to rapidly manufacture drugs for other cancers.
The ultrafast process can shave weeks off production by bypassing steps that traditionally have been manufacturing bottlenecks: Instead of isolating T cells from a patient's blood, Wald introduces the cancer-targeted receptors to the entire blood sample. And instead of growing T cells in culture before infusing them back into the patient, he harvests and infuses the cells right away.
UF-Kure19 is the first drug he has produced with the pared-down process. It costs about $10,000 to make a UF-Kure19 infusion—95% cheaper than manufacturing the CAR-T cell drugs in the market today, Wald said.
The clinical trial for UF-Kure19 began in 2023, a collaboration of three of Wald's colleagues at the medical school and cancer center. Principal investigator Changchun Deng, MD, PhD, an associate professor and UH oncologist, began the work with Koen van Besien, MD, PhD, a professor and director of the Wesley Center for Immunotherapy at , and Paolo Caimi, MD (MGT '24), an associate professor and a staff physician at .
The first phase of the trial included 10 patients from UH, Cleveland Clinic and the University of Iowa Holden Comprehensive Cancer Center.
Despite some skepticism that a drug made by the ultrafast process would work as well as other CAR-T cell drugs, early results hint that UF-Kure19 might be safer and more effective than those therapies. "We're seeing ... similar or better outcomes and less of the side effects," Wald said.
Initially, van Besien, who treated the trial's first patient, was skeptical that simply changing how a drug is produced would alter how it works in the body. But now he is cautiously optimistic that UF-Kure19 could become a new standard for treating many of the patients who come into his office: "The results have been so encouraging that I'm enthusiastic about it now," he said. "It's been an excellent surprise."
Illustration by Gordon Studer