Researchers at the University of Minnesota have completed a first human trial that proves a technique of edition of CRISPR/CAS9 genes to help the immune system to fight gastrointestinal advanced cancers (GI). The results, recently published in Lancet Oncology, show encouraging signs of safety and potential effectiveness of treatment.
“Despite many advances in the understanding of genomic drivers and other factors that cause cancer, with few exceptions, colorectal cancer in stage IV remains a large incurable disease,” said Emil Lou, MD, PHD, a gastrointestinal oncologist with the Faculty of Medicine of the University of Minnesot rehearsal. “This trial brings a new approach to our research laboratories to the clinic and shows potential to improve the results in patients with late stage disease.”
In the study, the researchers used edition of the CRISPR/CAS9 gene to modify an immune cell type called tumor infiltrating lymphocytes (TIL). By deactivating a gene called Cish, the researchers found that modified TIL were better able to recognize and attack cancer cells.
The treatment was tested in 12 highly metastatic patients in the terminal stage and it was found that they were generally safe, without serious side effects of gene edition. Several patients in the trial saw the growth of their arrested cancer, and a patient had a complete response, which means that in this patient, metastatic tumors disappeared over the course of several months and have not returned in more than two years.
“We believe that CISH is a key factor that prevents T cells from recognizing and eliminating tumors,” said Branden Moriarity, PHD, associate professor at the Faculty of Medicine at the University of Minnesota, researcher at the Masonic Cancer Center and co -director of the Genome Engineering Center. “Because it acts inside the cell, it cannot be blocked using traditional methods, so we turn to CRISPR -based genetic engineering.”
Unlike other cancer therapies that require continuous doses, this edition of genes is permanent and integrated in T cells from the beginning.
“With our gene editing approach, control point inhibition is achieved in one step and is permanently connected to T cells,” said Beau Webber, PHD, a professor associated with the researcher at the Faculty of Medicine at the University of Minnesota and the researcher at the Masonic Cancer Center.
The research team delivered more than 10 billion designed TIL without adverse side effects, demonstrating the viability of genetic engineering until sacrificing the ability to cultivate them to large quantities in the laboratory in a clinically compatible environment, which had never been done before.
While the results are promising, the process is still expensive and complex. Efforts are being made to rationalize production and better understand why therapy worked so effectively in the patient with a complete response to improve the focus on future tests.
This research was funded by Inima Bioscience.