City of Hope CAR-T scientist Christine Brown and team receive $12.8 million grant from California’s stem cell agency to fund trial for brain cancerOctober 4, 2017
City of Hope
The grant funds a phase 1 CAR-T trial targeting an aggressive brain cancer, malignant glioma
DUARTE, Calif. — City of Hope, a world-renowned cancer treatment and research center, today announced that a research team led by Christine Brown, Ph.D., and a clinical team headed by Behnam Badie, M.D., chief of neurosurgery, has received a $12.8 million grant from the California Institute for Regenerative Medicine (CIRM) to fund a phase 1 chimeric antigen receptor (CAR)-T cell trial targeting an aggressive brain cancer called malignant glioma, which includes glioblastoma. The trial will be open to adults and children.
CAR-T cells, a type of immunotherapy, are a cell-based therapy in which a patient’s own T cells are reprogrammed to actively seek out and destroy malignant cells. Few effective therapies currently exist for malignant glioma, which has a five-year survival rate of only 5.5 percent.
“Brain tumors are one of our biggest challenges in oncology, which is why City of Hope is focusing our efforts on finding better therapies,” said Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of City of Hope’s T Cell Therapeutics Research Laboratory, which is leading the institution’s CAR-T trials. “We have already made significant strides in finding more effective treatments, and City of Hope is extremely grateful that CIRM has recognized how crucial and urgent it is to support more research on malignant glioma and give patients better options and hope.”
City of Hope is the first and only cancer center treating patients with CAR-T cells targeting the IL13Rα2 antigen, a protein that is found on the cell surface of a majority of glioblastomas. It was also the first to administer CAR-T therapy locally in the brain, either by direct injection to the tumor site or through infusion into the cerebrospinal fluid through the ventricular system or both.
In addition, City of Hope researchers recently reported in the New England Journal of Medicine on the successful treatment of a patient with recurrent multifocal glioblastoma using CAR-T therapy to effectively attack cells with the IL13Rα2 antigen. A patient was treated with his own genetically modified CAR-T cells, using central memory T cells, a stem cell-like subset of immune cells; his multifocal glioblastoma regressed completely and clinical remission was sustained for 7.5 months.
For the upcoming CIRM-funded trial, a patient’s central memory T cells will be collected and reengineered to express the CAR. These CAR-T cells are then infused back into a patient and they are programmed to target a molecular marker expressed by glioma, including cancer stem cells. Memory T cells also remain in the patient's system for a longer period and have the potential to grow a reservoir of cancer-killing cells that can attack and destroy future glioma tumor cells.
Malignant glioma is difficult to treat due to several factors. The brain’s anatomy, which is encased in the skull, has a tough membrane layer and the blood-brain barrier, a semipermeable membrane, prevents easy access of potentially effective therapeutic drugs to the tumors. Malignant gliomas are also highly invasive, making their surgical removal difficult. Furthermore, heterogeneous stem-cell like tumor cells are resistant to current therapies, such as chemotherapy and radiation, which can lead to recurrence.
The CIRM-funded trial will make it possible for City of Hope to extend its clinical trial for patients to receive the CAR-T cells infused into the cerebrospinal fluid and a combined treatment in which patients receive them at the tumor site and cerebrospinal fluid.
“City of Hope is working hard to take this therapy to the next level for patients by finding new delivery methods and honing on which method and combination works best,” said Brown, the Heritage Provider Network Professor in Immunotherapy and associate director of the T Cell Therapeutics Research Laboratory at City of Hope. “We urgently need more effective therapies for our patients with malignant gliomas, and we will not give up until we find them.”
City of Hope, with its clinical, research and production facilities all on one campus, is uniquely positioned to lead such trials. Few institutions are capable of harnessing the same comprehensive “bench to bedside” resources necessary for the discovery, development, manufacturing, quality assurance, testing and deployment of leading-edge treatments.
In addition to Forman and Badie, other City of Hope research and medical collaborators participating on the new CIRM grant led by Brown include Michael Barish, Ph.D., chair and professor of Department of Developmental and Stem Cell Biology, Russell Rockne, director of Division of Mathematical Oncology, Vanessa Jonsson, Ph.D., assistant research professor, Darya Alizadeh, Ph.D., staff scientist, and M. Suzette Blanchard, Ph.D., associate research professor.
About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 49 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.