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University of Minnesota researchers have reported promising early results from a groundbreaking clinical trial using CRISPR/Cas9 gene-editing technology to treat advanced gastrointestinal (GI) cancers. The study, recently published in The Lancet Oncology, marks a significant milestone in the fight against stage IV colorectal and other GI cancers, which have historically been difficult to cure.
A New Approach to Cancer Immunotherapy
The clinical trial, led by Dr. Emil Lou of the University of Minnesota Medical School and Masonic Cancer Center, focused on enhancing the body’s immune response to cancer. Researchers collected tumor-infiltrating lymphocytes (TILs)-a type of immune cell-from patients and used CRISPR/Cas9 to deactivate a gene called CISH. This gene normally acts as a brake on the immune system, preventing T cells from fully attacking cancer cells.
“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,” Dr. Lou explained. “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.”
Encouraging Results in Early Trial
The phase 1 trial enrolled 12 patients with highly metastatic, end-stage GI cancers. The modified TILs were expanded in the lab and then infused back into the patients. The therapy was generally well-tolerated, with no serious side effects attributed to the gene-editing process.
Several patients experienced a halt in the progression of their cancer. Most notably, one patient achieved a complete response: their metastatic tumors disappeared within months and have not returned for over two years.
“We believe that CISH is a key factor preventing T cells from recognizing and eliminating tumors,” said Dr. Branden Moriarity, co-director of the Center for Genome Engineering at the University of Minnesota. “Because it acts inside the cell, it couldn’t be blocked using traditional methods, so we turned to CRISPR-based genetic engineering.”
Permanent and Precise
Unlike many cancer therapies that require repeated treatments, this gene-editing approach creates a permanent change in the patient’s immune cells. “With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells,” explained Dr. Beau Webber, another key researcher on the project.
The team successfully delivered more than 10 billion engineered TILs to patients without adverse effects, demonstrating the feasibility of producing these cells at scale in a clinical setting.
Next Steps and Future Potential
While these initial results are promising, the researchers caution that the process is still costly and complex. Efforts are underway to streamline production and to better understand why the therapy was so effective in the patient who achieved a complete response. The hope is to refine the approach and expand its effectiveness in future trials.
Disclaimer:
This article is based on early-stage clinical research published in The Lancet Oncology and reported by Medical Xpress on May 2, 2025. The therapy discussed is experimental and not yet widely available. Results from small, early-phase trials may not be replicated in larger studies. Patients should consult their healthcare providers before considering any new or experimental treatments.
For more information, see the original study: Emil Lou et al., “Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial,” The Lancet Oncology (2025). DOI: 10.1016/S1470-2045(25)00083-X
