City of Hope shares in $8 million Prostate Cancer Foundation award to develop CAR T cell therapy for advanced prostate cancer

The inaugural award will help develop clinic-ready CAR T therapies

LOS ANGELES, Dec. 7, 2022 /PRNewswire/ -- City of Hope, one of the largest cancer research and treatment organizations in the United States, today announced it has received, along with other leading cancer centers, an $8 million Therapy ACceleration To Intercept CAncer Lethality (TACTICAL) award from the Prostate Cancer Foundation to develop clinic-ready chimeric antigen receptor (CAR) T cell therapies for advanced prostate cancer that can overcome the therapy's current limitations.

"City of Hope is one of only a few cancer centers nationwide who currently have a CAR T trial for prostate cancer, so this is welcome news to us and bolsters our mission to provide effective CAR T therapies for solid tumors," said Saul Priceman, Ph.D., City of Hope assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation and associate director of Translational Sciences & Technologies in the T Cell Therapeutics Research Laboratory. He will lead the research with Tanya Dorff, M.D., City of Hope's section chief, Genitourinary Disease Program.

"Our goal is for this research to lead to a powerful new arsenal of immunotherapy treatments for advanced prostate cancer patients that can also treat racially diverse populations and advance immunotherapy in patients with other types of solid tumors," Dorff added.

The award, which spans three years and is shared by principal investigators at University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia and the National Cancer Institute, is one of four inaugural Class of 2022 PCF TACTICAL Awards. The $30 million program will support cross-disciplinary pioneering research toward the goal of developing 21^st century therapies for the most life-threatening form of prostate cancer.

With more than 70 CAR T therapy clinical trials and more than 1,000 patients treated with the therapy, City of Hope is a leader in this immunotherapy. In 2019, City of Hope started a phase one CAR T trial for prostate stem cell antigen (PSCA)-positive castration-resistant prostate cancer patients. The trial, which also received Prostate Cancer Foundation support and includes the National Cancer Institute as a collaborator, uses a CAR T cell developed by City of Hope that targets PSCA in prostate cancer. The trial is in its final stages of enrolling patients.

CAR T cells are a powerful type of immunotherapy in which a patient's own T cells are engineered to target and kill the cancer. The therapy has demonstrated efficacy and cures in patients with various blood cancers, including lymphomas, certain types of leukemia and multiple myeloma.

In prostate cancer, the efficacy and longevity of CAR T cells is limited by an immuno-suppressive tumor microenvironment. City of Hope and external collaborators have previously identified multiple genes in T cells that, when deleted, may improve tumor-killing potential and overcome the suppressive tumor microenvironment. 

For this project, City of Hope and external collaborators will comprehensively test the effects of deleting these genes in CAR T cell preclinical models. The team will also apply advanced analytic technologies to define the tumor and immune factors that impact CAR T cell therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC) in order to identify new therapeutic targets for improving CAR T efficacy.

CAR T cells are engineered to target tumor-associated antigens, such as PSMA and PSCA in prostate cancer, as in City of Hope's trial. City of Hope and external collaborators will identify new target antigens in African American and racially diverse prostate cancer populations, as well as in neuroendocrine-variant tumors, and test the efficacy of CAR T cells targeting these new antigens in preclinical models.

The efficacy of CAR T cells in solid tumors is also limited by genomic heterogeneity and loss of the target antigen. To overcome this barrier, the team will develop and test a "polytherapy" that combines CARs against multiple targets.

If successful, the team will launch a clinical trial testing the most promising CAR T clinical candidates and strategies within three years.

City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. As an independent, National Cancer Institute-designated comprehensive cancer center, City of Hope brings a uniquely integrated model to patients, spanning cancer care, research and development, academics and training, and innovation initiatives. Research and technology developed at City of Hope has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. A leader in bone marrow transplantation and immunotherapy, such as CAR T cell therapy, City of Hope's personalized treatment protocols help advance cancer care throughout the world.

With a goal of expanding access to the latest discoveries and leading-edge care to more patients, families and communities, City of Hope's growing national system includes its main Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and Cancer Treatment Centers of America. City of Hope's affiliated family of organizations includes Translational Genomics Research Institute and AccessHope™. For more information about City of Hope, follow us on Facebook, Twitter, YouTube, Instagram and LinkedIn.

SOURCE City Of Hope