CAR-T PSCA Therapy: A New Hope for Castration-Resistant Prostate Cancer

Castration-resistant prostate cancer (mCRPC) presents a major challenge for healthcare professionals. Despite recent advances, treatment options for this deadly disease remain limited. CAR-T therapy, which involves modifying immune cells to specifically target and destroy cancer cells, has shown promise; however, its effectiveness against solid tumors has yet to be confirmed. This study explores the potential of CAR-T cells in treating mCRPC, specifically targeting the Prostate Stem Cell Antigen (PSCA). The primary objective is to assess the efficacy, safety, and potential effects of this approach in addressing the unmet therapeutic needs of patients with mCRPC.

CAR-T PSCA Therapy: Results And Initial Clinical Observations

In this study, 14 patients with significant PSCA expression and advanced mCRPC were divided into three cohorts, each receiving increasing doses of PSCA CAR-T cells, with some patients undergoing prior lymphodepletion (LD):

• Cohort DL1: 100 million CAR-T cells without lymphodepletion.
• Cohort DL2: 100 million CAR-T cells with standard lymphodepletion.
• Cohort DL3: 100 million CAR-T cells with reduced lymphodepletion.

The primary endpoint was safety, specifically the occurrence of dose-limiting toxicities (DLTs).

The results showed an antitumor response in 4 out of 14 patients, with a 30% reduction in prostate-specific antigen levels. Dynamic changes in the composition of peripheral blood T cells confirmed immune system activation. Radiographic improvements in some participants indicated a reduction in tumor mass. Additionally, a moderate cytokine release syndrome was observed, without severe neurological or immune toxicity. Overall, CAR-T therapy was well tolerated, with grade 3 cystitis being the most common DLT.

Toward Optimizing CAR-T Therapies in mCRPC

These findings demonstrate that CAR-T cells targeting the PSCA antigen represent a promising therapeutic approach for mCRPC. Besides inducing an effective antitumor response, the safety profile is acceptable. These results lay the groundwork for optimizing dosages and combination strategies to enhance CAR-T cell persistence. Future directions for this therapy could include adjustments in lymphodepletion, development of next-generation CAR-T cells, and exploration of additional antigen targets to maximize benefits for patients resistant to current treatments.