In contrast, universal CAR-T therapies like WU-CART-007 are manufactured from the cells of healthy donors. These cells can be processed in large batches, frozen, and stored at hospitals, ready for immediate use as soon as a patient needs them. This approach not only saves critical time but also ensures that the "starting material" for the drug comes from a healthy immune system rather than one compromised by cancer and chemotherapy.
To make this universal application possible, the researchers employed CRISPR gene-editing technology to solve two major biological hurdles: graft-versus-host disease and "fratricide."
In GvHD, donor T-cells recognize the patient’s healthy tissues as foreign and attack them. By using CRISPR to delete the T-cell receptor from the donor cells, the researchers essentially "blinded" the cells to the patient’s healthy tissue, significantly reducing the risk of a dangerous immune rejection.
The second hurdle, fratricide, is unique to treating T-cell cancers. Because the therapeutic CAR-T cells are themselves T-cells, and they are engineered to target a protein called CD7 found on cancerous T-cells, they would naturally attack and kill each other during the manufacturing process. To prevent this "CAR-T cell fratricide," the researchers used CRISPR to remove the CD7 protein from the therapeutic cells themselves. This allows the WU-CART-007 cells to ignore one another while remaining laser-focused on destroying the CD7-positive cancer cells in the patient’s body.
A Collaborative Effort for Future Treatment
The development of WU-CART-007 represents a successful synergy between academic research and biotechnology entrepreneurship. The therapy was developed by Wugen, a biotech startup based in St. Louis that was founded by DiPersio and other investigators from WashU Medicine, including Matthew Cooper, PhD. Cooper, who formerly served on the WashU faculty, is now the chief scientific officer at Wugen. The company was launched in 2018 in collaboration with Washington University’s Office of Technology Management (OTM).
The success of this phase 1/2 trial has already paved the way for more extensive clinical investigation. A larger, international trial is currently underway to further validate these findings across a broader patient population and to track long-term outcomes.
"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," DiPersio said. If the results continue to hold, WU-CART-007 could become the first of its kind to provide a standard, readily available solution for a group of patients who, until now, had very little reason for hope.
