CAR T Cell Therapy for Advanced Prostate Cancer Shows Positive Phase 1 Results

Treating prostate cancer with immunotherapy has long been a challenge. Yet, promising preliminary results have emerged from a first-in-human phase 1 trial using a chimeric antigen receptor (CAR) T cell therapy. Developed by researchers at City of Hope, one of the nation's prominent cancer research and treatment organizations, this study shows potential in managing advanced prostate cancer with minimal side effects. The findings were published in Nature Medicine.

Under the guidance of Saul Priceman, Ph.D., associate professor in the Department of Hematology & Hematopoietic Cell Transplantation, and Tanya Dorff, M.D., section chief of the Genitourinary Disease Program, the trial focused on 14 prostate cancer patients. These patients had metastatic castration-resistant prostate cancer (mCRPC), a severe form of cancer that spreads beyond the prostate and resists hormone treatments. In the United States alone, over 34,000 men succumb to this type of cancer annually.

The innovative CAR T cell therapy targets the prostate stem cell antigen (PSCA), a protein highly expressed in prostate cancer cells. By extracting T cells from the patient's bloodstream and reprogramming them to recognize and attack cells expressing PSCA, the treatment aims to eliminate cancer cells effectively. The reprogrammed T cells were then reintroduced into the patient's system to carry out their therapeutic function.

One of the primary challenges in treating prostate cancer with immunotherapy is the tumor microenvironment, which is often described as an "immune desert." This means that the environment within the tumor is not conducive to the infiltration of T cells, making it difficult for immunotherapies to work effectively. Dr. Dorff emphasized the significance of their study, stating that the CAR T cell therapy developed at City of Hope could be a crucial step toward overcoming this challenge.

The primary objective of the trial was to assess the safety and determine the dose-limiting toxicities of the therapy, along with a preliminary evaluation of its efficacy. Results showed that patients received a single infusion of 100 million CAR T cells without undergoing the usual lymphodepletion chemotherapy, which is commonly used to improve CAR T cell efficacy in blood cancers. This was a critical assessment since it was the first time CAR T cells were used in human prostate cancer patients.

However, at the same CAR T cell dose with lymphodepletion, some patients experienced cystitis, or bladder irritation. This side effect likely occurred because PSCA is also present in bladder cells, which the CAR T cells inadvertently attacked. To address this, a new cohort was introduced with reduced lymphodepletion, mitigating this toxicity.

Among the 14 patients, four exhibited declines in their PSA levels, a marker for disease progression in prostate cancer, with one patient showing a significant decrease. Imaging also demonstrated therapeutic responses in some patients. Additionally, five patients experienced mild to moderate cytokine release syndrome (CRS), a common and treatable side effect of CAR T cell therapy.

A notable observation was that CAR T cells did not persist at high levels beyond the 28-day monitoring period, limiting the therapy's long-term effectiveness. Researchers plan to tackle this issue in a follow-up trial that is now open for enrollment.

One particularly encouraging case involved a patient who had undergone multiple prior therapies. This patient experienced a 95% reduction in PSA levels and a noticeable decline in cancer in both bones and soft tissues, maintaining this positive response for about eight months. Dr. Dorff expressed gratitude for the patient's participation and emphasized the need to continue refining the therapy to enhance its effectiveness.

City of Hope remains at the forefront of CAR T cell therapy research, treating nearly 1,500 patients since the inception of its CAR T program in the late 1990s. With approximately 70 ongoing CAR T clinical trials, including those for 13 different solid tumor types, City of Hope continues to be a leader in this innovative field. The institution manufactures its CAR T cells at its dedicated facility, the Cell Therapy Production Center, located on its Los Angeles campus.