A pioneering international clinical trial has revealed that a new type of immunotherapy, designed to target some of the most aggressive and hard-to-treat blood cancers, is producing remarkable remission rates in patients who have exhausted all other medical options. Led by researchers at Washington University School of Medicine in St. Louis, the phase 1/2 trial suggests that this "off-the-shelf" treatment could transform the landscape of care for T-cell malignancies, offering a vital bridge to curative procedures for patients previously deemed terminal.
The study, published May 30 in the journal Blood, focused on a specific and innovative form of CAR-T cell immunotherapy. Unlike traditional CAR-T treatments, which have seen significant success in B-cell cancers, this new therapy—known as WU-CART-007—is engineered to confront the unique challenges of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). For the patients enrolled in this trial, the stakes could not have been higher; most had seen their cancer return after multiple rounds of intensive chemotherapy or failed stem cell transplants.
"For patients with these rare and aggressive cancers, who have no other options, this has the potential to become a transformative advance in the field," said the study’s senior author, John F. DiPersio, MD, PhD. DiPersio, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine, originally developed the foundational technology for the therapy in his laboratory. "The trial demonstrated a high likelihood of response to the therapy and even remission. This CAR-T cell treatment shows promise in becoming a ‘bridge-to-transplant’ therapy for patients who would otherwise not be eligible for stem cell transplantation, which is the only potentially curative treatment for these blood cancers."
Addressing an Unmet Clinical Need
The prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma is historically dismal. In the United States, approximately 1,000 people are diagnosed with these specific cancers annually. While initial treatments can be effective for some, those whose cancer does not respond—or those who suffer a relapse after treatment—face a survival window that averages only six months. Statistics show that fewer than 7% of such patients are still living five years after their diagnosis.
The primary difficulty in treating these cancers lies in the nature of the T-cells themselves. T-cells are a cornerstone of the human immune system, responsible for identifying and destroying pathogens and abnormal cells. When these cells become cancerous, they are notoriously difficult to target without simultaneously destroying the healthy immune system. Furthermore, because standard CAR-T therapies use a patient’s own T-cells as the "chassis" for the drug, the manufacturing process for T-cell cancers is fraught with technical hurdles, including the risk of contaminating the final product with the patient’s own cancerous cells.
The WU-CART-007 trial included 28 participants, ranging from adolescents to adults, all of whom suffered from T-ALL or T-LBL that had either failed to respond to initial treatments or had recurred after multiple lines of standard therapy. The trial was conducted across an international network of sites in Australia, Europe, and the United States, with the St. Louis site based at the Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine.
Clinical Efficacy and the "Bridge to Transplant"
The trial was structured with a dose-escalation phase, a standard clinical protocol designed to identify the maximum tolerated dose that provides the highest efficacy with the most manageable side effects. This phase is critical in determining the safety profile of a new biological agent. In the second phase of the trial, 13 patients received the full recommended dose of 900 million CAR-T cells.
Before receiving the immunotherapy, patients underwent a procedure known as lymphodepletion. This preparatory chemotherapy regimen clears out the patient’s existing immune cells, essentially "making room" for the newly infused therapeutic CAR-T cells to expand, multiply, and begin their search-and-destroy mission against the cancer.
The results among the evaluable patients were striking. Of the 11 patients who could be fully assessed following the treatment at the target dose, the overall response rate reached 91%. This means that nearly every patient in that group saw a significant reduction in their cancer burden or showed no remaining signs of the disease. Specifically, eight out of those 11 patients (72.7%) achieved a complete remission.
"These response and remission rates—ranging from 70%-90% of patients—are much higher than we would expect from standard-of-care for this cancer type, which typically leads to remission in only 20%-40% of patients," said Armin Ghobadi, MD, the study’s first and corresponding author. Ghobadi is a professor of medicine and the clinical director of the Center for Gene and Cellular Immunotherapy at WashU Medicine. "These responses are remarkable because the patients in this trial had run out of options. They had very aggressive cancers return after several lines of therapy, including several who relapsed after an earlier stem cell transplant."
Perhaps most importantly, the therapy allowed several patients to stabilize long enough to undergo a stem cell transplant. At the time of the study’s data cutoff, six patients who moved on to a transplant remained in remission, with no evidence of disease, six to 12 months after the procedure. This "bridge-to-transplant" capability is vital, as many patients with aggressive leukemia are often too sick or have too high a disease burden to survive the transplant process without first achieving a state of remission.
Safety and Side Effect Management
While the efficacy of WU-CART-007 was high, the researchers also closely monitored the side effects common to CAR-T cell therapies. The most frequent adverse event was cytokine release syndrome (CRS), which occurred in 88.5% of the patients. CRS is a systemic inflammatory response triggered when the infused CAR-T cells become highly active and release a flood of cytokines into the bloodstream.
Most cases of CRS in the trial were classified as mild or moderate, though approximately 19% of patients experienced more severe symptoms. These symptoms can include high fevers, low blood pressure, and respiratory issues, but they were generally manageable with existing medical protocols. A smaller subset of patients experienced rarer side effects, including neurotoxicity syndrome and low-grade graft-versus-host disease (GvHD). Two patients in the study passed away due to complications from their cancer or treatment-related infections, underscoring the high-risk nature of both the disease and the intensive therapeutic interventions required to treat it.
Off-the-shelf cell therapy
One of the most significant technological breakthroughs of the WU-CART-007 therapy is its "universal" or "off-the-shelf" nature. Most currently approved CAR-T therapies are autologous, meaning they are manufactured using a patient’s own blood cells. This requires a logistical odyssey: cells must be collected from the patient, shipped to a central manufacturing facility, genetically engineered over several weeks, and then shipped back to the hospital for infusion. For patients with rapidly progressing T-cell leukemia, this three-to-six-week wait time can be a death sentence.
In contrast, universal CAR-T therapies like WU-CART-007 are manufactured from the cells of healthy donors. These cells can be processed in large batches, frozen, and stored at hospitals, ready for immediate use as soon as a patient needs them. This approach not only saves critical time but also ensures that the "starting material" for the drug comes from a healthy immune system rather than one compromised by cancer and chemotherapy.
To make this universal application possible, the researchers employed CRISPR gene-editing technology to solve two major biological hurdles: graft-versus-host disease and "fratricide."
In GvHD, donor T-cells recognize the patient’s healthy tissues as foreign and attack them. By using CRISPR to delete the T-cell receptor from the donor cells, the researchers essentially "blinded" the cells to the patient’s healthy tissue, significantly reducing the risk of a dangerous immune rejection.
The second hurdle, fratricide, is unique to treating T-cell cancers. Because the therapeutic CAR-T cells are themselves T-cells, and they are engineered to target a protein called CD7 found on cancerous T-cells, they would naturally attack and kill each other during the manufacturing process. To prevent this "CAR-T cell fratricide," the researchers used CRISPR to remove the CD7 protein from the therapeutic cells themselves. This allows the WU-CART-007 cells to ignore one another while remaining laser-focused on destroying the CD7-positive cancer cells in the patient’s body.
A Collaborative Effort for Future Treatment
The development of WU-CART-007 represents a successful synergy between academic research and biotechnology entrepreneurship. The therapy was developed by Wugen, a biotech startup based in St. Louis that was founded by DiPersio and other investigators from WashU Medicine, including Matthew Cooper, PhD. Cooper, who formerly served on the WashU faculty, is now the chief scientific officer at Wugen. The company was launched in 2018 in collaboration with Washington University’s Office of Technology Management (OTM).
The success of this phase 1/2 trial has already paved the way for more extensive clinical investigation. A larger, international trial is currently underway to further validate these findings across a broader patient population and to track long-term outcomes.
"We must complete this larger trial first, but we are hopeful this universal CAR-T cell therapy can become an approved treatment for patients with deadly T-cell cancers," DiPersio said. If the results continue to hold, WU-CART-007 could become the first of its kind to provide a standard, readily available solution for a group of patients who, until now, had very little reason for hope.
