City of Hope receives CIRM grant to develop T cell-based immunotherapy against glioma

City of Hope was granted a $5,217,004 early translational research award by the California Institute for Regenerative Medicine (CIRM) to support the development of a T cell-based immunotherapy that re-directs a patient's own immune response against glioma stem cells. City of Hope has been awarded more than $49.7 million in grant support from CIRM since awards were first announced in 2006.    

City of Hope is a pioneer in T cell immunotherapy research, helping to develop genetically modified T cells as a treatment for cancer. This strategy, termed "adoptive T cell therapy," focuses on redirecting a patient's immune system to specifically target tumor cells, and has the potential to become a promising new approach for treatment of cancer.

"In this research, we are genetically engineering a central memory T cell that targets proteins expressed by glioma stem cells," said Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of the T Cell Immunotherapy Research Laboratory. "Central memory T cells have the potential to establish a persistent, lifelong immunity to help prevent brain tumors from recurring."

The American Cancer Society estimates that more than 22,000 people in the U.S. will be diagnosed with a brain tumor this year, and 13,700 will die from the disease. Glioma is a type of brain tumor that is often difficult to treat and is prone to recurrence. Currently, less than 20 percent of patients with malignant gliomas are living five years after their diagnosis. This poor prognosis is largely due to the persistence of tumor-initiating cancer stem cells, a population of malignant cells similar to normal stem cells in that they are able to reproduce themselves indefinitely. These glioma stem cells are highly resistant to chemotherapy and radiation treatments, making them capable of re-establishing new tumors.

Researchers at City of Hope previously have identified several proteins as potential prime targets for the development of cancer immunotherapies, such as interleukin 13 receptor alpha 2, a receptor found on the surface of glioma cells, and CD19, a protein that is active in lymphoma and leukemia cells. Both investigational therapies are currently in phase I clinical trials. Forman is the principal investigator for the newly granted study which will develop a T cell that targets different proteins expressed by glioma stem cells. Christine Brown, Ph.D., associate research professor, serves as co-principal investigator, and Michael Barish, Ph.D., chair of the Department of Neurosciences, and Behnam Badie, M.D., director of the Brain Tumor Program, serve as co-investigators on the project.

"Because cancer stem cells are heterogeneous, our proposed therapy will target multiple antigens to cast as wide a net as possible over this malignant stem cell population," said Brown.

"While in this effort, we are targeting a neurological cancer, our approach will lead to future studies targeting other cancers, including those that metastasize to the brain," added Barish.

"The CIRM grant will help us to build a targeted T cell therapy against glioma that can offer lasting protection, determine the best way to deliver the treatment, establish an efficient process to manufacture these T cells for treatment, and get approval for a human clinical trial," said Badie.