An innovative "universal" CAR-T cell immunotherapy has demonstrated remarkable efficacy against aggressive T cell cancers in an international Phase I/II clinical trial, achieving a 91% overall response rate in patients with limited treatment options. The therapy, called WU-CART-007, represents a significant advancement for patients with rare and deadly blood cancers who have exhausted standard treatment approaches.
The trial, led by researchers at Washington University School of Medicine in St. Louis and published May 30 in the journal Blood, evaluated 28 adult and adolescent patients with T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma that had either relapsed after multiple treatment lines or never responded to initial therapy. These aggressive cancers affect approximately 1,000 people annually in the United States, with patients surviving only six months on average when standard treatments fail, and less than 7% remaining alive at the five-year mark.
Exceptional Response Rates in Treatment-Resistant Patients
Of the 11 patients who received the full dose of 900 million CAR-T cells and could be evaluated after treatment, 10 patients either showed no signs of cancer or experienced significant reduction in cancer cell burden. Eight patients (72.7%) achieved complete remission, with six who underwent subsequent transplantation remaining in remission with no evidence of disease six to 12 months later.
"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 first and corresponding author Armin Ghobadi, MD, a professor of medicine and 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."
Revolutionary "Off-the-Shelf" Manufacturing Approach
Unlike approved CAR-T cell therapies that must be manufactured from each patient's own immune cells—a process requiring three to six weeks—WU-CART-007 represents a "universal" approach that can be produced from healthy donor cells and stored frozen for immediate use. This breakthrough was made possible through CRISPR gene editing technology, which removes the T cell receptor from donor cells to prevent graft-versus-host disease and eliminates the risk of CAR-T cell fratricide, where therapeutic cells attack each other.
The therapy was developed by Wugen, a Washington University biotech startup founded by senior author John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine, along with other university investigators. The clinical trial was conducted across multiple sites in Australia, Europe, and the United States, with the St. Louis component taking place at Siteman Cancer Center.
Addressing Unique Technical Challenges
The development of WU-CART-007 required overcoming significant technical hurdles specific to T cell cancers. Since both the therapeutic cells and cancer cells are T cells, researchers had to prevent the CAR-T cells from attacking one another—a complication not present in approved CAR-T therapies that target B cell cancers. After using CRISPR to modify the cells and prevent harmful side effects, the therapeutic cells are engineered to target CD7, a protein on the surface of cancerous T cells.
Manageable Safety Profile
The therapy demonstrated a manageable safety profile, with most patients (88.5%) experiencing cytokine release syndrome—a common side effect of CAR-T cell therapy where immune cells release chemicals causing inflammatory responses. The majority of these cases were mild or moderate, with approximately 19% of patients experiencing more severe cytokine release syndrome. A small number of patients experienced rarer side effects including neurotoxicity syndrome and low-grade graft-versus-host disease, all of which were managed with additional therapies.
Clinical Implications and Future Directions
"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 DiPersio. "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."
A larger international clinical trial of WU-CART-007 is already underway to further evaluate the therapy's potential. While larger studies with more patients and longer follow-up are necessary to determine whether this therapy could be curative on its own, the initial results provide hope for patients facing these devastating diagnoses with previously limited treatment options.
