Article
Press Release
Author(s):
Saul Priceman, PhD
Treating prostate cancer with immunotherapy is currently difficult to do. But preliminary results from a first-in-human phase 1 trial using a chimeric antigen receptor (CAR) T cell therapy developed by researchers from City of Hope®, one of the largest cancer research and treatment organizations in the United States, showed that patients with advanced prostate cancer had minimal side effects with the cellular immunotherapy and had promising therapeutic activity, according to a study published today in Nature Medicine.
The trial treated 14 prostate stem cell antigen (PSCA)-positive patients who had metastatic castration-resistant prostate cancer (mCRPC), which had spread beyond the prostate and no longer responded to hormone treatment, using CAR T cell therapy. More than 34,000 men with this type of prostate cancer die each year in the United States.
Saul Priceman, PhD, City of Hope associate professor, Department of Hematology & Hematopoietic Cell Transplantation, and team developed CAR T cells that target prostate stem cell antigen (PSCA) found to be highly expressed in prostate cancer. The treatment took a patient’s immune cells – known as T cells – from the bloodstream, and reprogrammed the cells in a laboratory with a CAR to recognize and attack the PSCA protein on the surface of cancer cells. CAR T cells were then infused back into the patient’s system to destroy cancer cells.
“Prostate cancer has been called an immune desert — the tumor microenvironment is difficult to treat with immunotherapies because you don’t get a lot of T cells inside the tumor,” said Tanya Dorff, MD, City of Hope section chief, Genitourinary Disease Program, and professor, Department of Medical Oncology & Therapeutics Research. “It takes something really powerful to overcome that. Our study showed that City of Hope’s CAR T cell therapy for prostate cancer could be a step closer to doing that.”
“Our trial’s preliminary major finding is that PSCA-directed CAR T cells may be effective against mCRPC,” Priceman added. “This opens up the opportunity to continue to develop this type of cellular immunotherapy for these patients, who currently have no other effective treatment options.”
The trial’s goals were to examine the therapy’s safety and dose-limiting toxicities, or side effects that limit the amount of treatment that can be administered, as well as preliminary data on the treatment’s efficacy in patients.
The study’s findings were:
One patient who had received several prior therapies responded well to the CAR T cell therapy. His PSA level decreased by 95% and cancer in his bones and soft tissue also declined. He experienced this positive response for approximately eight months.
“The patient’s results were very encouraging, and we are deeply grateful for his participation in our study as well as other patients and their families,” Dorff said. “We want to continue with this therapy and increase the amount of CAR T cells, and continue to carefully monitor for any health problems, as we think this can improve the therapy’s effectiveness.”
The phase 1b trial using the PSCA-CAR T cell therapy in combination with radiation to enhance anti-tumor activity aims to enroll up to 24 patients.
City of Hope, a recognized leader in CAR T cell therapies, has treated nearly 1,500 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 about 70 ongoing CAR T clinical trials, which include 13 different solid tumor types. The trials use City of Hope-developed therapies and industry-sponsored products. A recent study published in Nature Medicine featured City of Hope’s CAR T cell therapy for brain tumors.
City of Hope manufactured the CAR T cells in its own facility, the Cell Therapy Production Center on its Los Angeles campus.
The Prostate Cancer Foundation helped fund the trial.
Saul Priceman, PhD, and Tanya Dorff, MD, and their teams worked together on the phase 1 clinical trial using a City of Hope-developed CAR T cell therapy for prostate cancer.