A pioneering form of immunotherapy targeting some of the most aggressive and difficult-to-treat blood cancers has demonstrated significant clinical promise, coupled with a manageable safety profile, according to new findings from an international phase 1/2 clinical trial. Led by researchers at Washington University School of Medicine in St. Louis, the study highlights a potential paradigm shift for patients who have historically faced a very poor prognosis after failing standard treatment regimens.
The clinical trial focused on the safety and efficacy of an innovative CAR-T cell immunotherapy designed specifically to combat cancerous T cells. Unlike many existing immunotherapies that target B cell malignancies, this new approach addresses T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphoblastic lymphoma (T-LBL). These are rare but highly aggressive forms of cancer that often become resistant to conventional chemotherapy. For the participants in this trial, the experimental therapy represented a final hope, as they had exhausted all available standard treatment options without success.
The results of the trial, published May 30 in the journal Blood, suggest that this new therapeutic avenue could provide a much-needed lifeline. Among the study participants who received the highest planned dose of the engineered cells, the vast majority achieved full remission, a result that has energized the oncology community and the researchers involved in the therapy’s development.
Senior author John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine, emphasized the gravity of the situation for these patients. DiPersio, who originally developed the technology in his laboratory, noted that for those with rare and aggressive cancers who have run out of options, this therapy has the potential to become a transformative advance in the field of hematologic oncology. He pointed out that the trial demonstrated not only a high likelihood of initial response but also the achievement of durable remissions in a significant portion of the cohort.
One of the most critical aspects of the study is the role of this CAR-T treatment as a "bridge-to-transplant." In the current landscape of blood cancer treatment, a stem cell transplant remains the only potentially curative option for many patients. However, many patients with T-ALL or T-LBL are ineligible for such transplants because their disease is too advanced or they cannot achieve a deep enough remission through standard chemotherapy to make a transplant viable. By inducing remission where other drugs failed, this new immunotherapy opens the door for these patients to receive life-saving stem cell transplants.
Despite the excitement surrounding these early results, the research team remains cautious. They noted that while the initial data is compelling, larger studies involving a broader patient population and longer-term follow-up are essential. Such studies will be necessary to determine if the therapy can be curative on its own or if its primary role will remain as a bridge to other definitive treatments like transplantation.
The scope of the challenge addressed by this trial is significant. Approximately 1,000 people are diagnosed with T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma annually in the United States. For those whose cancer does not respond to initial treatment—or for those who suffer a relapse after an initial period of health—the outlook is traditionally grim. On average, these patients survive only six months, and the five-year survival rate is a sobering 7%.
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.
Off-the-shelf cell therapy
A defining characteristic of WU-CART-007 is its status as a "universal" or "allogeneic" CAR-T cell therapy. Most CAR-T therapies currently approved by the FDA are autologous, meaning they are manufactured using a patient’s own immune cells. This process requires collecting the patient’s cells, shipping them to a specialized manufacturing facility to be genetically engineered, and then shipping them back for infusion. This cycle can take anywhere from three to six weeks—a timeframe that many patients with aggressive, fast-moving leukemias simply do not have.
In contrast, the universal CAR-T cells evaluated in this trial are created using CRISPR gene editing technology and are derived from the cells of healthy donors. This allows the therapy to be manufactured in large batches, frozen, and stored for immediate use. This "off-the-shelf" availability significantly reduces the waiting period for patients, allowing them to begin treatment almost immediately after they are deemed eligible.
The use of CRISPR technology is central to making this universal approach work. When using donor cells, there is a high risk of graft-versus-host disease, where the donor’s T cells perceive the patient’s healthy tissues as foreign and attack them. To prevent this, the researchers used CRISPR to delete the T cell receptor from the donor cells.
Furthermore, the researchers had to solve a biological puzzle unique to T cell cancers: "fratricide." In standard CAR-T therapies for B cell cancers, the engineered T cells target a protein found on B cells. However, in this trial, both the treatment (T cells) and the target (cancerous T cells) share similar markers. Without further modification, the therapeutic CAR-T cells would identify each other as the enemy and destroy one another before they could reach the cancer. By using CRISPR to remove a specific antigen from the therapeutic cells, the researchers prevented them from attacking each other, ensuring they remained viable long enough to eliminate the cancer.
After these complex genetic modifications, the cells are further engineered to target a protein called CD7, which is prominently displayed on the surface of cancerous T cells. Once infused, these "predator" cells seek out and destroy any cell expressing CD7.
The success of this phase 1/2 trial has already paved the way for the next stage of clinical development. DiPersio confirmed that a larger, international clinical trial is currently underway to further validate these findings. While the completion of this larger trial is a prerequisite for regulatory approval, the research team is optimistic that this universal CAR-T cell therapy could eventually become a standard, approved treatment for patients facing the most deadly forms of T cell cancer.
