Prostate stem cell antigen (PSCA) (PSCA)

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein and a member of the Ly-6/uPAR family [1]. While its exact physiological role is not fully elucidated, it is implicated in cell signaling, adhesion, and proliferation [2]. PSCA is significantly overexpressed in prostate cancer, particularly in high-grade, metastatic, and castration-resistant cases, as well as in pancreatic and bladder malignancies [2, 3]. Its restricted expression in normal tissues—primarily the prostate, bladder, and stomach—makes it an attractive target for chimeric antigen receptor (CAR) T-cell therapy [3, 5]. In this context, an engineered single-chain variable fragment (scFv) is used to redirect T cells to recognize PSCA-expressing tumor cells, leading to targeted cell lysis [3]. Clinical candidates like BPX-601 are currently being evaluated to treat solid tumors expressing PSCA, though researchers must carefully manage potential on-target, off-tumor toxicities in the gastrointestinal and urinary tracts [4, 5].

Other names

PRO232Prostate stem cell antigen precursor

The single-chain variable fragment (scFv) of the CAR-T cell specifically binds to the extracellular domain of the Prostate stem cell antigen (PSCA) on the surface of malignant cells [3]. This binding event triggers the aggregation of the CAR molecules, leading to the phosphorylation of intracellular signaling domains (such as CD3-zeta and co-stimulatory domains like 4-1BB or CD28), which activates the T cell to release cytotoxic granules (perforin and granzymes) and inflammatory cytokines, ultimately resulting in the lysis of the target tumor cell [3, 5].