Gene-editing therapy shows promise against advanced colorectal cancer

The CRISPR/Cas9 gene-editing technique has shown promise in fighting advanced colorectal cancer, according to results of the first-in-human clinical trial published in The Lancet Oncology. 

The trial shows encouraging signs of the safety and potential effectiveness of the treatment against metastatic gastrointestinal (GI) cancers.

In the study, researchers used CRISPR/Cas9 gene-editing to modify a type of immune cell called tumour-infiltrating lymphocytes (TILs).

They deactivated a gene called CISH and found that modified TILs were better able to recognise and attack 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,” said Emil Lou, a gastrointestinal oncologist with the University of Minnesota Medical School.

“We believe that CISH is a key factor preventing T cells from recognising and eliminating tumours,” added Branden Moriarity, Associate Professor at the varsity.

Moriarity explained that as CISH acts inside cells, it couldn`t be blocked using traditional methods. So the team used CRISPR-based genetic engineering to block it.

The treatment was tested in 12 highly metastatic, end-stage patients and found to be generally safe, with no serious side effects from the gene editing.

Several patients in the trial saw the growth of their cancer halt, and one patient had a complete response. In this patient, the metastatic tumour disappeared over several months and did not return for over two years.

Unlike other cancer therapies that require ongoing doses, this gene edit is permanent and built into the T cells from the start.

“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,” Lou said.

The research team delivered more than 10 billion engineered TIL without adverse side effects, demonstrating the feasibility of genetically engineering TIL without sacrificing the ability to grow them to large numbers in the lab in a clinically compliant environment, which has never been done before.

While the results are promising, the process remains costly and complex, said the researchers while calling for a better understanding of why the therapy worked so effectively.

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