New CRISPR-Based Therapy Shows Promise in Treating Advanced GI Cancers
The results suggest the therapy is both safe and potentially effective.
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Researchers at the University of Minnesota have conducted a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique aimed at enhancing the immune system’s ability to fight advanced gastrointestinal (GI) cancers.
The results, published in Lancet Oncology, suggest the therapy is both safe and potentially effective.
A new approach to treating stage IV colorectal cancer
Despite significant progress in understanding the genetic and molecular factors contributing to cancer, stage IV colorectal cancer remains largely incurable.
Dr. Emil Lou, a gastrointestinal oncologist with the University of Minnesota Medical School, Masonic Cancer Center, and M Health Fairview, emphasized the trial's potential to bring new treatment options to patients with late-stage cancer.
“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,” said Lou, who was the clinical principal investigator for the trial.
Targeting immune cells with CRISPR/Cas9
In this study, researchers used CRISPR/Cas9 technology to modify a type of immune cell known as tumor-infiltrating lymphocytes (TILs). Specifically, they deactivated a gene called CISH to enhance the TILs' ability to recognize and attack cancer cells. The gene-editing technique proved successful in making the TILs more effective at targeting tumors, potentially offering a new therapeutic pathway for fighting GI cancers.
Trial results: safety and effectiveness
The treatment was tested in 12 patients with highly metastatic, end-stage GI cancers, and the results were promising. The therapy was generally safe, with no serious side effects observed from the gene editing. Several patients showed no further cancer growth, and one patient experienced a complete response. In this patient, metastatic tumors disappeared within several months and have not returned in over two years.
Dr. Branden Moriarity, an associate professor at the University of Minnesota and co-director of the Center for Genome Engineering, noted the significance of the gene CISH, which prevents T cells from recognizing and eliminating tumors. Traditional therapies could not block this gene, which led researchers to explore CRISPR-based genetic modifications as a novel strategy.
A one-time treatment
Unlike other cancer therapies that require ongoing doses, this gene-editing approach is designed to provide permanent modification to the T cells. Dr. Beau Webber, an associate professor at the University of Minnesota Medical School, highlighted the advantage of the therapy, stating, “With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells.”
Challenges and next steps
Although the early results of the therapy are encouraging, the process remains complex and costly. The research team delivered more than 10 billion engineered TILs without adverse side effects, demonstrating the feasibility of producing large quantities of genetically modified T cells in a clinically compliant environment – an important achievement for advancing the therapy. However, the team is focused on improving production methods and understanding why the therapy worked so well for the patient with a complete response, aiming to refine the approach for future trials.
This research was supported by Intima Bioscience.
Reference: Lou E, Moriarity B, Webber B, et al. CRISPR-based gene-editing therapy shows promise in advanced gastrointestinal cancer. Lancet Oncol. 2025. doi:10.1016/j.lanonc.2025.03.009
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