U of M opens first of its kind Phase I/II clinical trial to treat metastatic gastrointestinal epithelial cancer using CRISPR edited immune cells
The University of Minnesota has opened a new and innovative clinical trial for the treatment of metastatic gastrointestinal epithelial cancer. The Phase I/II clinical trial, which will use the revolutionary CRISPR/Cas9 System, has opened exclusively at the M Health Fairview University of Minnesota Medical Center.
This trial comes on the heels of groundbreaking research from University of Minnesota researchers who reported for the first time the use of CRISPR for editing a novel intracellular checkpoint called Cytokine-Induced SH2 protein (CISH) to increase the capability of tumor-infiltrating lymphocytes (TIL) to fight cancer.
Principal Investigators Branden Moriarity, PhD, Beau Webber, PhD, and R. Scott McIvor, PhD, of the University of Minnesota Medical School and the Masonic Cancer Center, University of Minnesota, in collaboration with researchers at the National Cancer Institute’s Surgery Branch and their respective teams, utilized CRISPR/Cas9 technology to delete a gene called CISH in human T cells.
“We knew that CISH was a key factor preventing T cells from recognizing and eliminating tumors, but because it resides inside the cell we couldn’t block it in the same fashion as other checkpoint molecules,” noted Dr. Moriarity. “Developing a drug to effectively target it would take years, if it were possible at all, which is why we turned to CRISPR/Cas9 based genome engineering.”
Webber, Moriarity, and collaborators found that inactivating CISH at the genetic level significantly increased the ability of T cells known as tumor-infiltrating lymphocytes (TILs) to recognize and kill cancer cells forming tumors in mice.
“Existing checkpoint therapies require repeated dosing and are often limited by the tumor environment that surrounds immune cells,” added Dr. Webber. “With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells.”
The clinical trial, sponsored by Intima Capital, will be led at the University of Minnesota by Emil Lou, MD, PhD, FACP, Associate Professor of Medicine at the Medical School in the Division of Hematology, Oncology, and Transplantation and Medical Director of the Cancer Center’s Clinical Trials Office-Solid Tumor Unit.
“In this study, surgery will be done to remove pieces of a patient’s tumor,” noted Dr. Lou, Principal Investigator for the clinical trial. “The pieces of the tumor will then be used to identify and grow T cells that can recognize unique and important changes in the patient’s cancer cells. Then, these selected T cells will be treated with CRISPR/Cas9 to inactivate the CISH gene. In this way, not only are more cells given back to the patient, but the cells will also have a greater chance of killing the tumors.”
The patient-specific CRISPR-engineered T cells will be produced and manufactured at the University of Minnesota’s Molecular and Cellular Therapeutics (MCT) facility, which offers full-service development and manufacturing of cell- and tissue-based products, monoclonal antibodies, and other therapeutic proteins, as well as active pharmaceutical ingredients for use in Phase I, II or III clinical trials. The MCT is one of only five such centers in the country. M Health Fairview, the clinical partner of the Masonic Cancer Center, supports the MCT in the production of these molecules.
About the Masonic Cancer Center, University of Minnesota
The Masonic Cancer Center, University of Minnesota, is the Twin Cities’ only Comprehensive Cancer Center, designated ‘Outstanding’ by the National Cancer Institute. As Minnesota’s Cancer Center, we have served the entire state for more than 25 years. Our researchers, educators, and care providers have worked to discover the causes, prevention, detection, and treatment of cancer and cancer-related diseases. Learn more at cancer.umn.edu.
About the University of Minnesota Medical School
The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. Learn how the University of Minnesota is innovating all aspects of medicine by visiting www.med.umn.edu.