Tn-glycosylated Podoplanin (Tn-PDPN)

Tn-glycosylated Podoplanin (Tn-PDPN) is a tumor-specific glycoform of the podoplanin protein, characterized by the presence of the Tn antigen (N-acetylgalactosamine linked to serine or threonine) on its extracellular domain. This aberrant glycosylation typically results from mutations in the COSMC chaperone, which is essential for proper O-glycan elongation, leading to the exposure of truncated glycans that are absent in healthy tissues (Ju and Cummings, 2002). While wild-type podoplanin is expressed in the lungs, kidneys, and lymphatic system, Tn-PDPN is exclusively found in various malignancies, including squamous cell carcinomas, glioblastomas, and mesotheliomas (Kato et al., 2016). It plays a critical role in cancer progression by interacting with the platelet receptor CLEC-2 to induce platelet aggregation, which facilitates hematogenous metastasis and immune evasion (Suzuki-Inoue et al., 2011). Therapeutic targeting of Tn-PDPN and other Tn-bearing glycoproteins (such as Tn-MUC1 or Tn-TFRC) using cancer-specific monoclonal antibodies (CasMabs) or chimeric antigen receptor (CAR) T cells offers a high degree of tumor selectivity (He et al., 2019). These agents selectively recognize the Tn-glycopeptide epitope, potentially avoiding the 'on-target off-tumor' toxicities associated with targeting the widely expressed non-glycosylated protein backbone. Furthermore, targeting multiple Tn-bearing glycoproteins simultaneously may reduce the risk of tumor escape due to antigen loss (He et al., 2019).

Other names

AggrusT1-alphagp36PA2.26OTS8Glycoprotein 36PodoplaninCancer-specific PodoplaninTn-glycosylated proteinsTumor-associated carbohydrate antigens (TACAs)

Inhibition of platelet aggregation by blocking the PDPN-CLEC-2 interaction; induction of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC); and direct T-cell mediated lysis of Tn-positive tumor cells via chimeric antigen receptor (CAR) engagement.