The therapy used in the trial, known as WU-CART-007, was developed by Wugen, a biotechnology startup based in St. Louis. The company was founded by DiPersio and other investigators from WashU Medicine, including Matthew Cooper, PhD. Cooper, who co-founded the company while serving on the WashU Medicine faculty and now acts as Wugen’s chief scientific officer, worked alongside the university’s Office of Technology Management (OTM) to launch the venture in 2018. This collaboration between academic research and commercial biotechnology allowed the therapy to move from the lab into a global clinical setting.
The trial was a massive international undertaking, with clinical sites spanning Australia, Europe, and the United States. In St. Louis, the clinical work was centered at the Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, providing local patients with access to this cutting-edge science.
The trial was structured with a dose-escalation phase, a standard protocol in early-stage clinical trials designed to find the optimal balance between efficacy and safety. This phase allowed researchers to determine the maximum dose of CAR-T cells that patients could tolerate while maintaining manageable side effects. Following this determination, thirteen patients were administered the full dose of 900 million CAR-T cells.
Before receiving the immunotherapy, patients underwent a procedure known as lymphodepletion. This process uses chemotherapy to temporarily clear out the patient’s existing immune cells, essentially creating a biological "space" for the newly introduced therapeutic T cells to engraft, expand, and begin their attack on the cancer. While the procedure is a standard part of CAR-T therapy, it is not without risks. During the study period, two patients in the cohort passed away due to complications from their cancer or the treatment process, such as infections.
However, the efficacy data among the evaluable patients was striking. Out of 11 patients who could be fully evaluated after the treatment, the overall response rate reached 91%. This means that 10 out of the 11 patients saw a significant reduction in their cancer cell burden or showed no remaining signs of the disease. Specifically, eight of those 11 patients, or 72.7%, achieved a state of complete remission. By the time the data was cut off for the study, six patients who had transitioned to a stem cell transplant remained in remission, showing no evidence of disease six to 12 months later.
Armin Ghobadi, MD, a professor of medicine and clinical director of the Center for Gene and Cellular Immunotherapy at WashU Medicine, served as the first and corresponding author of the study. He noted that the response and remission rates observed—ranging from 70% to 90%—far exceed what is typically seen with the current standard of care. Standard treatments for these aggressive relapsed cancers usually lead to remission in only 20% to 40% of cases. Ghobadi described the responses as "remarkable," particularly given that the participants were often in the final stages of their disease and had relapsed even after previous stem cell transplants.
As with any intensive immunotherapy, side effects were a significant consideration. The most common adverse event was cytokine release syndrome (CRS), which affected 88.5% of the patients. CRS occurs when the infused CAR-T cells become highly active and release a flood of chemicals called cytokines into the bloodstream, triggering a systemic inflammatory response. While most of these cases were classified as mild or moderate, approximately 19% of the patients experienced more severe forms of the syndrome. Other, rarer side effects included neurotoxicity and low-grade graft-versus-host disease (GvHD). However, the researchers noted that these adverse events were generally manageable through the use of additional medical therapies.
