Innovative Immunotherapy Shows Promise Against Aggressive T Cell Cancers

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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WashU Medicine
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