13 August 2019 - - Saul Priceman, Ph.D., City of Hope's assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation, and his research team have received a USD 9.28m award from the California Institute for Regenerative Medicine to support a chimeric antigen receptor T cell phase 1 clinical trial for the treatment of women with HER2-positive breast cancer that has spread to the brain, US-based biomedical research and treatment centre City of Hope said.

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 and 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 specialist 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 programmes 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 and 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.