Massive breakthrough: Gene-edited immune cells halt growth of stage IV gastrointestinal cancers in trial patients

In a quiet Minnesota clinic, a scientific leap just reshaped the future of cancer therapy. Researchers at the University of Minnesota have completed a landmark first-in-human clinical trial using CRISPR/Cas9 gene editing to supercharge the immune system against aggressive gastrointestinal (GI) cancers.

The findings, published in The Lancet Oncology, hint at a new frontier in the fight against some of the deadliest forms of cancer—with one patient seeing their tumours vanish entirely for over two years.

"Despite many advances in understanding the genomic drivers and other factors causing cancer, with few exceptions, stage IV colorectal cancer remains a largely incurable disease," said Emil Lou, MD, PhD, a gastrointestinal oncologist with the University of Minnesota Medical School, Masonic Cancer Center and M Health Fairview, and clinical principal investigator for the trial. "This trial brings a new approach from our research labs into the clinic and shows potential for improving outcomes in patients with late-stage disease."

In the study, scientists used CRISPR/Cas9 to edit tumor-infiltrating lymphocytes (TILs) — immune cells that naturally enter tumors. By switching off a gene known as CISH, the edited TILs gained a stronger ability to detect and kill cancer cells.

No serious side effects from the gene editing were reported. Some saw their disease stabilise, and notably, one patient experienced a complete response: their metastatic tumors disappeared and have not returned in over two years.

"We believe that CISH is a key factor preventing T cells from recognizing and eliminating tumors," Branden Moriarity, PhD, associate professor at the University of Minnesota Medical School and co-director of the Center for Genome Engineering, told phys.org. "Because it acts inside the cell, it couldn't be blocked using traditional methods, so we turned to CRISPR-based genetic engineering."

Unlike therapies that require repeated treatments, this one-off edit is permanent.

"With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells," said Beau Webber, Ph.D., associate professor at the University of Minnesota Medical School and Masonic Cancer Center researcher.

More than 10 billion edited TILs were delivered to each patient without adverse side effects. The team also proved they could grow large volumes of these edited cells in a clinical-grade lab setting — a critical step never before achieved at this scale.

Despite the encouraging signs, challenges remain. The process is costly and complex, and researchers are now working to streamline production and understand why the treatment led to a full remission in one patient, with the goal of replicating those results in future trials.