Prostate cancer (PC) is the most common cancer in men and poses significant therapeutic challenges due to its low mutational burden, limiting conventional immunotherapy. Targeted immunotherapy, particularly Chimeric Antigen Receptor (CAR) T cells, has shown promise. CAR-T cells, engineered to express specific CAR proteins, enhance tumor cell recognition and eradication. However, CAR-T cells face obstacles in solid tumors, including antigen heterogeneity, off-tumor toxicities, and limited infiltration.
This study investigated PST1, an overexpressed antigen in prostate cancer. PST1, due to its critical role in cancer cell invasion and metastasis, presents a promising target for therapeutic intervention in prostate cancer. We developed second-generation CAR-T cells targeting PST1, incorporating a humanized antigen-recognition domain and 4-1BB co-stimulatory signaling.
In vitro assays showed that PST1-specific CAR-T cells exhibited strong antigen-dependent cytotoxicity against prostate cancer cells, reducing cell viability and proliferation. In vivo studies in murine models confirmed these CAR-T cells effectively targeted and eradicated PST1-expressing tumors, prolonging survival and reducing tumor burden.
Our findings highlight PST1 as a viable target for prostate cancer immunotherapy. The development of PST1-targeting CAR-T cells shows significant potential for clinical application, offering a novel therapeutic approach. Further studies are needed to optimize efficacy and safety, paving the way for future clinical trials.