New gene-editing therapy from MCC researchers shows early success in fighting advanced GI cancers
MCC's mission to reduce the burden of cancer on Minnesotans and beyond means that we are constantly searching for, creating, and evaluating new methods for treating the toughest cancers out there. Recently, a group of our Masonic Cancer Center scientists developed a new treatment that uses gene editing to help the immune system fight advanced gastrointestinal (GI) cancers, such as colon, stomach, and pancreatic cancers. This treatment is currently being safely used in a clinical trial and has shown early signs of success! The results of the trial were recently published in Lancet Oncology and offer additional details on the potential effectiveness of the treatment.
Below, we catch up with Drs. Lou, Moriarity, and Webber to chat about the study and its impact.
How the treatment works
Our immune system uses special cells called T cells to find and destroy harmful invaders like viruses and cancer cells. However, some cancers can hide from T cells, making them harder to eliminate.
Researchers discovered that a gene called CISH inside T cells can act like a brake, preventing them from attacking cancer effectively. Using a gene-editing tool called CRISPR, scientists removed the CISH gene from T cells, allowing the T cells to better recognize and kill 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 MCC's Dr. Emil Lou, a gastrointestinal oncologist at the University of Minnesota (U of M) Medical School and the lead scientist for the trial. Dr. Lou adds, “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.”
The treatment process
Doctors remove a tumor sample from the patient.
They identify and grow T cells from the tumor that can recognize the cancer.
Using CRISPR, they delete, or edit out, the CISH gene from these T cells.
The edited T cells are multiplied in the lab.
The patient undergoes chemotherapy to prepare their body.
The edited T cells are infused back into the patient to attack the cancer.
The treatment was tested in 12 highly metastatic, end-stage patients—meaning their cancer had spread from its original location to another part of the body, and all other treatment options had been exhausted. In these patients, the treatment was 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, meaning that, in this patient, the metastatic tumors disappeared over the course of several months and have not returned in over two years.
“We believe that CISH is a key factor preventing T cells from recognizing and eliminating tumors,” said MCC's Dr. Branden Moriarity, associate professor at the U of M Medical School and co-director of the Center for Genome Engineering. He adds, “Because it acts inside the cell, it couldn’t be blocked using traditional methods, so we turned to CRISPR-based genetic engineering.”
Unlike other cancer therapies that require ongoing doses, this gene edit is permanent and built into the T cells from the start.
“With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells,” said MCC's Dr. Beau Webber, associate professor at the U of M Medical School.
The research team delivered more than 10 billion engineered T cells without adverse side effects. For Drs. Lou, Moriarity, Webber, and team, this demonstrated that it is possible to genetically engineer the T cells without sacrificing the ability to grow them in large numbers in the lab's clinically compliant environment, which has never been done before.
What's next?
This trial is for patients with advanced GI cancers that haven't responded to standard treatments. While the results of this study are promising, the process remains costly and complex. Efforts are underway to streamline production and better understand why the therapy worked so effectively in the patient with a complete response in order to improve the approach in future trials.
Thank you to all of our donors for continuing to fuel this work. Your generosity to the Masonic Cancer Center is what makes these kinds of groundbreaking research discoveries possible. Donate today to MCC's lifesaving cancer research.
This research was funded by Intima Bioscience. A version of this story was first published by the University of Minnesota Medical School.