Researchers from the University of Minnesota have carried out a first clinical trial to humans testing a CRISPR / CAS9 gene editing technique to help the immune system fight against advanced gastrointestinal cancers (GI). The results, recently published in Lancet Oncology, show encouraging signs of safety and potential efficiency of treatment.
“Despite numerous advances in understanding genomic engines and other factors causing cancer, with a few exceptions, colorectal cancer of stage IV 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 main clinical investigator for the trial. “This trial brings a new approach to our research laboratories in the clinic and shows potential to improve results in patients with an advanced disease. »»
In the study, the researchers used the editing of the CRISPR / CAS9 gene to modify a type of immune cell called lymphocytes infiltrating tumors (TIL). By deactivating a gene called CISH, the researchers found that the modified TIL were better able to recognize and attack cancer cells.
The treatment was tested in 12 highly metastatic and terminal patients and has generally proven to be safe, without serious side effects of the gene editing. Several trial patients have seen the growth of their cancer stop, and a patient had a complete response, which means that in this patient, metastatic tumors have disappeared in several months and have not returned for more than two years.
“We believe that Cish is a key factor preventing T cells from recognizing and eliminating tumors,” said Branden Moriarity, PHD, an associate professor at the University of Minnesota Faculty of Minnesota, researcher of Masonic Cancer Cancer and Codirector of the Center for Genome Engineering. “Because it acts inside the cell, it could not be blocked using traditional methods, so we turned to genetic genius based on Crispr. »»
Unlike other cancer therapies that require current doses, this gene modification is permanent and integrated into T cells from the start.
With our genetic editing approach, inhibition of the control point is accomplished in a single step and is permanent in T cells “”
Beau Webber, PHD, associate professor at the University of Minnesota Medicine School and researcher at the Masonic Cancer Center
The research team has delivered more than 10 billion ingenants to unwanted side effects, demonstrating the feasibility of genetically engineering without sacrificing the ability to grant them to a large number in the laboratory in a clinically compliant environment, which has never been done before.
Although the results are promising, the process remains expensive and complex. Efforts are underway to rationalize production and better understand why therapy has worked so effectively in the patient with a complete response in order to improve the approach of future trials.
This research was funded by Intima Bioscience.
