City of Hope Scientist Receives $9.28 Million for CAR T Cell Immunotherapy Clinical Trial for Patients With HER2-Positive Breast Cancer That Has Spread to the Brain

HER2 refers to a protein – human epidermal growth factor receptor-2 – which is found on the cell surface of breast cancer cells and drives cancer progression. About 20% of breast cancer patients are HER2-positive, according to the American Cancer Society.

The trial, which opened for enrollment in the fall of 2018 and whose lead clinical investigator is Jana Portnow, M.D., City of Hope associate clinical professor in the Department of Medical Oncology & Therapeutics Research, is testing the safety and effectiveness of the CAR T cell therapy for breast cancer patients with brain metastases who are not effectively being controlled with other therapies. It is estimated that nearly half of all women with HER2-positive breast cancer will eventually develop brain metastases.

“Our team’s goal is to develop a novel therapy for breast cancer patients with brain metastases who currently have no other effective treatments,” Priceman said. “This is a beautiful example of how early support from private donors and foundations helped to develop a therapy and initiate a trial we were desperate to bring to patients, and now this CIRM award funds the entire clinical trial and helps to leverage the knowledge gained here to further advance this therapy.”

CAR T cells are a cell-based type of 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. Patients receive CAR T cells directly to the ventricles of their brains, which is an administration route that was first attempted successfully at City of Hope. City of Hope patents covering the HER2 CAR were licensed to Mustang Bio in 2017.

City of Hope, a recognized leader in CAR T cell therapies, has treated more than 350 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 20 ongoing CAR T cell clinical trials, and has just initiated trials for patients with solid tumors, including prostate cancer.

The trial’s key investigators include City of Hope’s Stephen J. Forman, M.D., director, T Cell Therapeutics Research Laboratory and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation; Christine Brown, Ph.D., deputy director, T Cell Therapeutics Research Laboratory and the Heritage Provider Network Professor in Immunotherapy; and Behnam Badie, M.D., chief of City of Hope’s Division of Neurosurgery and Heritage Provider Network Professor in Gene Therapy. The award also includes City of Hope’s Russel Rockne, Ph.D., Vanessa Jonsson, Ph.D., Ammar Chaudhry, M.D., as well as collaborations with University of Southern California’s Peter Kuhn, Ph.D., and California Institute of Technology’s Lior Pachter, Ph.D.

CIRM funded early preclinical work related to this study, which was important in optimizing the therapy for the eventual Food and Drug Administration approval for permission to start a clinical trial. City of Hope also highlights Eli Khouri, Steve Meringoff, Zach Horowitz, Jody and Gary Marsh, The Kenneth T. and Eileen L. Norris Foundation and Gateway for Cancer Research for their support of this program.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked one of America’s “Best Hospitals” in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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