Successfully combining cellular therapy and gene therapy in a mouse model system, researchers at UCLA’s Jonsson Comprehensive Cancer Center (JCCC) have developed a viable treatment strategy for breast cancer that has metastasized, or spread, to the patient’s brain. The laboratory study was led by Carol Kruse, professor of neurosurgery, Cancer Center member and member of the UCLA Brain Research Institute. The study was published in the journal Clinical Cancer Research on August 1, 2013.
Breast cancer is the most common form of cancer in women, and metastasis is a major cause of health deterioration and death from the disease. Management of metastasis is difficult for several reasons. The circulatory network of the brain, known as the “blood-brain barrier,” prevents many anti-cancer drugs from reaching areas to which a cancer has spread. Also, the tendency of metastasis to spring up in multiple places in the brain simultaneously makes current treatments, such as radiation, challenging.
Cellular therapy is a type of immunotherapy, or treatment that involves the immune system, that uses T cells. These “foot soldiers of the immune system” are sensitized in the laboratory to kill breast cancer cells, and then the T cells are injected into the part of the brain to which the cancer has spread. The research shows the T cells move through tissue and can then recognize and directly kill the tumor cells.
With gene therapy, cancer cells are killed by a drug called 5-flurocytosine (5-FC). To get the gene into the cancer cells, the researchers first insert the gene into a virus that can penetrate and spread among the tumor cells. After the virus has infected the cells, nontoxic 5-FC is given to the patient. Tumor cells infected by the virus convert the nontoxic drug to a toxic form that kills the cancer cells. Dr. Noriyuki Kasahara, a professor in the department of medicine, developed the gene therapy method in his laboratory.
While the two methods alone each show efficacy in mouse models, the greatest reduction in metastatic brain tumor size happened when the cellular and gene therapies were combined.
“There is a significant lack of federally funded research addressing translational studies on brain metastases of systemic cancers even though metastatic brain tumors occur ten times more frequently than primary brain tumors in humans,” Dr. Kruse said. “These patients have a dismal prognosis because the brain represents a ‘sanctuary site’ where appropriate access by many chemotherapeutics is ineffective. Our research addresses this unmet need.”
Both experimental therapies are being tested individually in ongoing clinical trials for primary malignant brain tumors. These trials present a unique opportunity for rapid translation of this technology from the laboratory to the clinic in the treatment of breast cancer, and all other types of cancer that metastasize to the brain.
This research was supported by the U.S. Army Research Materiel Command, California Breast Cancer Research Program, National Center for Advancing Translational Sciences of the National Institutes of Health, UCLA Clinical Translational Science Institute, Joan S. Holmes Memorial Research Fund, Joan S. Holmes Memorial Postdoctoral Fellowship and Tocagen, Inc.
