Podocalyxin-like protein 1 (PODXL) (PODXL)

Podocalyxin-like protein 1 (PODXL), frequently identified by its carbohydrate epitope TRA-1-60, is a heavily glycosylated type I transmembrane sialomucin and a member of the CD34 family of proteins. It is a well-established marker of pluripotency in human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), where it plays a role in maintaining an undifferentiated state and regulating cell-cell contacts. In oncology, PODXL is overexpressed in various aggressive cancers, including prostate, breast, and germ cell tumors, where its expression correlates with increased metastatic potential and poor prognosis. The TRA-1-60 epitope is a specific keratan sulfate modification on the PODXL protein backbone that is highly specific to pluripotent and malignant cells, making it an attractive target for therapeutic intervention. Current drug development efforts include radiopharmaceutical therapies like Bstrongomab and chimeric antigen receptor (CAR) T-cell therapies, such as those utilizing the PcMab-6 clone, which are designed to selectively eliminate TRA-1-60-positive cancer stem cells. However, therapeutic targeting must account for the expression of PODXL in normal tissues, such as renal podocytes and vascular endothelial cells, to avoid off-target toxicities. The epitope recognized by the TRA-1-60 antibody is typically lost upon cell differentiation, providing a narrow window for targeting undifferentiated malignant cells. Research into cancer-specific monoclonal antibodies (CasMabs) aims to enhance the safety profile of these therapies by targeting tumor-specific glycosylation patterns. Overall, TRA-1-60/PODXL represents a promising target for precision medicine in aggressive and metastatic cancers.

Other names

TRA-1-60TRA-1-60 antigenPodocalyxinPCLP-1Gp200GCTM-2 antigenTRA-1-60(R)TRA-1-60(S)

Targeted cell ablation via radiopharmaceutical therapy or CAR-T cell-mediated cytotoxicity