Researchers are reporting encouraging outcomes from an early-stage clinical trial of a new immunotherapy designed to combat aggressive blood cancers. The treatment, which targets cancerous T cells, demonstrated significant efficacy with manageable side effects, according to findings presented by an international team lead by scientists at Washington University School of Medicine in St.Louis.

The clinical trial focused on a CAR-T cell immunotherapy engineered to specifically target and destroy malignant T cells. Participants were individuals diagnosed with rare forms of cancer,specifically T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma,for whom standard treatments had failed. The majority of patients in the study who received the full dose of the new immunotherapy experienced complete remission.

The results of the trial were published May 30 in the journal Blood.

CAR-T Therapy as a Bridge to Transplant

“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 frist 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 or else not be eligible for stem cell transplantation, which is the only potentially curative treatment for these blood cancers.”

Larger studies are underway to assess the therapy’s potential for long-term remission or cure.

The initial trial involved 28 adult and adolescent patients with relapsed or treatment-resistant T cell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma. Approximately 1,000 individuals are diagnosed with these cancers each year in the U.S. The prognosis for patients whose cancer does not respond to initial treatment or returns after treatment is poor, with an average survival of only six months and a five-year survival rate of less than 7%.

The experimental therapy, known as WU-CART-007, was created by Wugen.The clinical trial was conducted at sites in Australia, Europe, and across the U.S., including at Siteman Cancer Center in St. Louis.

“These responses are remarkable as the patients in this trial had run out of options.”

trial Design and Outcomes

The clinical trial employed a dose-escalation design to determine the optimal dose of therapeutic cells. Thirteen patients received the full dose of 900 million CAR-T cells following lymphodepletion, a procedure to reduce the number of existing immune cells to facilitate the expansion of the therapeutic T cells. Two patients died during the study period due to their cancer or treatment-related complications.

Among the 11 patients evaluable for treatment response, the overall response rate was 91%, with 10 patients showing either no signs of cancer or a significant reduction in cancer cell burden. Complete remission was achieved in 72.7% of patients (8 out of 11). At the data cutoff, six patients who underwent a subsequent transplant remained in remission for six to 12 months.

“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.

The majority of patients (88.5%) experienced cytokine release syndrome (CRS),a common side effect of CAR-T cell therapy,with most cases being mild or moderate. Severe CRS occurred in approximately 19% of patients. Other less frequent side effects included neurotoxicity syndrome and low-grade graft-versus-host disease. Adverse events were managed with supportive therapies.

Global CAR-T Cell Therapy

The immunotherapy is a “universal” CAR-T cell therapy,meaning it can be produced from cells donated by any healthy individual and used to treat any patient with a T cell cancer. This contrasts with existing CAR-T cell therapies that are derived from a patient’s own immune cells, requiring a lengthy manufacturing process.Universal CAR-T cell therapies can be manufactured in advance and stored for immediate use.

The production process utilizes CRISPR gene editing to eliminate the T cell receptor from donor cells, minimizing the risk of graft-versus-host disease. Additional modifications prevent the CAR-T cells from attacking each other, a critical step given that both the therapeutic and cancerous cells are T cells. The engineered CAR-T cells target the CD7 protein on the surface of cancerous T cells.

“A larger international clinical trial of this therapy is already underway,” DiPersio said. “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.”