You may have heard of CAR T-cell therapy, a cancer treatment that involves removing immune cells from a patient and re-engineering them to become better cancer fighters, but have you heard of CAR M therapy?
Short for chimeric antigen receptor (CAR) macrophages, CAR M therapy is similar to CAR T, but instead of re-engineering T cells to find specific targets on a cancer cell, it modifies macrophages, specialized white blood cells that “eat” cell debris and foreign invaders, including cancer cells.
“CAR-T therapy works well in blood cancers, but it’s been more difficult to get it to work in solid tumors because solid tumors actively block T cells,” says University of Colorado Anschutz Cancer Center member Siddhartha Mitra, PhD. “Macrophages, on the other hand, are intrinsically designed to get into solid tumors. Our thought was to use that property of macrophages and combine it with CAR T-cell technology. Since the macrophage can get into a solid tumor, why not put a CAR in a macrophage and make the macrophage do what it normally does, which is to eat?”
Mitra recently received a three-year grant from the Matthew “Iron Matt” Larson Foundation for Pediatric Brain Tumorsto develop CAR M therapies to treat diffuse midline gliomas, a particularly deadly type of pediatric brain cancer.
“Diffuse midline gliomas are one of the worst tumors you can have,” says Mitra, assistant professor of pediatrics and neurosurgery in the CU Anschutz School of Medicine. “Surgeons don't touch it, because it's in a very critical part of the brain. You may be given some radiation, but it's more palliative, trying to make it easier to live.”
Working with cancer center collaborators including Eric Kohler, MD, PhD, Sujatha Venkataraman, PhD, Rajeev Vibhakar, MD, PhD, and Mercedes Rincon, PhD, Mitra and his team will develop and test the CAR Ms to destroy glioma cells, with the added aim of engineering the cells in such a way that they will secrete proteins called cytokines that will make the tumor microenvironment more welcoming to T cells.
“At the end of the day, T cells are the best killers. They're the most efficient immune cells,” says Mitra, a clinician at Children’s Hospital Colorado’s Center for Cancer and Blood Disorders. “Can we engineer the macrophage in such a way that not only it is eating and debulking the tumor, but also giving rise to a long-term T-cell response that then prevents the tumor from coming back?”
Mitra, who has a separate National Institutes of Health grant to develop CAR Ms for use in adult brain cancer patients, hopes that by the end of the three-year period for the grant funded by the Matthew Larson foundation, the new therapy will be ready for a clinical trial in patients — another step closer to helping young patients with the deadly cancer.
“Every time there's a new option, the hope is always that it helps them live longer and better lives,” he says. “I'm hoping that's where this will take us; that it's a more effective treatment for some of these more untreatable cancers.”