Women with HER2-positive breast cancer that has spread to the brain need more treatment options, and City of Hope and Mustang Bio Inc. are meeting that challenge. A new City of Hope chimeric antigen receptor (CAR) T cell trial - the first to focus on HER2-positive breast cancer patients with brain metastases - is now enrolling potential participants.
The phase 1 trial will be conducted in an outpatient setting and will also be the first to use intraventricular delivery of CAR T cells directly to the brains of these patients. It will test the safety and effectiveness of the CAR T cell therapy for patients who have tried other types of treatment that are no longer effective. HER2 refers to a cancer-causing protein called human epidermal growth factor receptor-2, which is found on the cell surface of breast cancer cells, as well as some lung, colon and other cancer cells, and some melanoma cells. About 20 percent of breast cancer patients are HER2-positive, according to the American Cancer Society.
"For a woman who already has breast cancer, learning that a brain tumor has developed can be a frightening diagnosis because there are few treatment options available. CAR T cell therapy may be another tool in our fight against this devastating disease," said Jana Portnow, M.D., City of Hope associate clinical professor in the Department of Medical Oncology & Therapeutics Research and associate director of the Brain Tumor Program. Portnow and Saul Priceman, Ph.D., assistant research professor in City of Hope's T cell immunotherapy program, who conducted preclinical research that led to the trial's development, are leading the CAR T cell trial.
"Our hope is that the HER2-specific CAR T cell therapy will target and kill HER2-positive cancer cells, and safely and effectively treat brain metastases in these patients," Priceman added.
CAR T cell therapy is a type of cell-based immunotherapy in which a patient's own T cells are reprogrammed to actively seek out and destroy cancerous cells. For this trial, the patient's T cells will be isolated from the blood and genetically engineered to express a CAR that allows these immune cells to target and eradicate HER2-positive cancer cells.
City of Hope, a recognized leader in CAR T cell therapies, has treated more than 200 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world - it currently has 16 ongoing CAR T clinical trials, including a trial that opened recently for patients with primary glioblastoma that expresses the HER2 protein. The institution plans to open a trial in the coming months for patients with bone metastatic prostate cancer.
Mustang Bio Inc., a company focused on the development of novel immunotherapies based on proprietary CAR T technology and gene therapies for rare diseases, licensed the HER2 technology from City of Hope in 2017.
The HER2 trial meets a crucial need - it is estimated that nearly half of all women with HER2-positive breast cancer will eventually develop brain metastases. The current standard of care for treating brain metastases uses HER2-targeted drugs and/or radiation.
"Targeted agents don't always work because of the blood-brain barrier, a semipermeable membrane that often prevents easy access of potentially effective therapeutic drugs to the tumors," Portnow said. "Likewise, radiation has its limitations in durably controlling disease. These patients are in desperate need of safe and more effective therapies."
City of Hope researchers were the first to use intraventricular delivery of CAR T cells in patients with glioblastoma, one of the deadliest types of brain tumors. They found that injecting engineered CAR T cells locally into a patient's brain, or regionally through infusion in the ventricular system, has the potential to eradicate brain tumors.
"Because this type of CAR T cell delivery was found to be safe, City of Hope will now also use this route of administration for patients on this trial," Priceman added.