Innovative Immunotherapy Shows Promise Against Aggressive T Cell Cancers

T cell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma are rare, aggressive blood cancers that affect around 1,000 people annually in the U.S. If the disease fails to respond to treatment or returns, the prognosis is bleak—patients survive only about six months on average, with fewer than 7% surviving five years. Now, a novel immunotherapy has shown promise in an international phase 1/2 clinical trial for treating these hard-to-treat T cell cancers.

The investigational therapy was developed by biotech company Wugen (St. Louis, MO, USA) and tested by a team of scientists led by Washington University School of Medicine in St. Louis (WashU Medicine, St. Louis, MO, USA). The treatment, WU-CART-007, is described as a “universal” CAR-T cell therapy. Unlike existing FDA-approved CAR-T therapies that require harvesting and engineering a patient’s own T cells, WU-CART-007 is manufactured using cells from healthy donors. This allogeneic approach, made possible by CRISPR gene editing, enables the treatment to be produced in advance, stored frozen, and used off-the-shelf for any patient with a T cell malignancy—potentially eliminating the typical 3–6 week wait associated with personalized CAR-T therapy. The therapy's design involves using CRISPR to delete the T cell receptor from donor cells, which significantly reduces the risk of graft-versus-host disease—a condition in which donor T cells attack the recipient’s healthy tissue. Additionally, the removal of another antigen prevents the CAR-T cells from mistakenly attacking each other, a problem unique to T cell therapies since both therapeutic and malignant cells share similar markers. After these edits, the cells are engineered to recognize and destroy cancerous T cells by targeting a surface protein called CD7.

The trial included 28 adolescents and adults with either T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma, all of whom had relapsed after multiple treatments or were refractory to standard therapy. In the dose-escalation phase, 13 patients received the highest tested dose of 900 million CAR-T cells following lymphodepletion, a preparatory step that clears space in the immune system for the new cells to thrive. Of these, two patients died from their cancer or treatment-related complications such as infection. Among the 11 evaluable patients, the overall response rate was 91%, with 10 patients showing either complete disappearance of the disease or significant reduction in cancer burden. Eight of those patients (72.7%) achieved complete remission. As of the latest data cut-off, six patients who received stem cell transplants remained in remission for six to 12 months. Cytokine release syndrome, a common side effect of CAR-T therapies, was reported in 88.5% of participants, though most cases were mild or moderate. Severe cases occurred in about 19% of patients. A few also experienced neurotoxicity and low-grade graft-versus-host disease. These side effects were managed with additional therapies. While early results are promising, the researchers caution that larger and longer-term studies are needed to assess whether WU-CART-007 could eventually serve as a curative treatment.

“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 senior author John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine, who first developed the therapy in his lab at WashU Medicine. “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.”

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