CRISPR Gene-Editing Therapy Shows Promise in Advanced GI Cancer Treatment

Researchers at the University of Minnesota have reported promising results from a pioneering clinical trial involving a CRISPR/Cas9 gene-editing technique aimed at enhancing the immune response against advanced gastrointestinal (GI) cancers. The findings, recently detailed in The Lancet Oncology, indicate both safety and potential effectiveness for this innovative therapy.

Despite significant advancements in understanding the genetic underpinnings of various cancers, stage IV colorectal cancer remains predominantly untreatable. Emil Lou, a gastrointestinal oncologist and clinical principal investigator for the trial, expressed optimism about the new treatment approach, which transitions from laboratory research to clinical application.

In this study, the research team utilized CRISPR/Cas9 technology to modify tumor-infiltrating lymphocytes (TILs), a type of immune cell. By disabling a specific gene known as CISH, the modified TILs exhibited an enhanced ability to identify and attack cancer cells effectively.

The trial involved 12 patients with highly metastatic, end-stage cancer, and overall, the gene editing was found to be safe without any serious adverse effects. Notably, some participants experienced stabilization in cancer growth, while one individual achieved a complete response, with metastatic tumors vanishing over several months and remaining absent for over two years.

Branden Moriarity, an associate professor at the University of Minnesota, noted that CISH plays a crucial role in hindering T cells from recognizing and destroying tumors. The innovative CRISPR-based genetic engineering approach allows for the modification of T cells that cannot be addressed through traditional methods.

Unlike conventional cancer therapies that require ongoing administration, this gene edit is permanent, embedded within the T cells from the outset. Beau Webber, another associate professor involved in the research, explained that this gene-editing method allows for immediate checkpoint inhibition, effectively integrating it into the T cells in a single step.

The team successfully administered over 10 billion engineered TILs without experiencing negative side effects. This achievement demonstrates the potential for large-scale genetic engineering of TILs in a clinically compliant environment, a feat previously unaccomplished.

While the outcomes are encouraging, the gene-editing process remains complex and expensive. Researchers are actively working to optimize production methods and to further investigate the factors contributing to the success of the treatment, particularly in the patient who achieved a complete response, with the aim of enhancing future trials.

For further details, refer to the full study titled "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" published in The Lancet Oncology.