de-N-acetyl-polysialic acid (dPSA)

De-N-acetyl-polysialic acid (dPSA) is a unique tumor-associated glycan derivative of polysialic acid (PSA) characterized by the removal of N-acetyl groups from its neuraminic acid residues [1, 11]. While standard PSA is primarily expressed during embryonic development, dPSA is aberrantly re-expressed on the surface of various malignant cells, including those in neuroblastoma, melanoma, and small cell lung cancer, while remaining largely absent from normal adult tissues [1, 5, 12]. It is frequently found in association with cell-surface nucleolin, where it plays a critical role in oncogenic processes such as cell adhesion, migration, and immune shielding (immune evasion) [2, 5]. Due to its high tumor specificity, dPSA is an attractive therapeutic target for precision oncology. Current therapeutic strategies include monoclonal antibodies like SEAM 3, which can induce apoptosis, and novel antibody-drug conjugates such as SAC-253 designed to deliver cytotoxic agents specifically to dPSA-positive tumors [5, 7].

Other names

dPSAde-N-acetyl PSANeuPSAneuraminic acid-containing polysialic acidde-N-acetylated polysialic acid

Drugs targeting de-N-acetyl-polysialic acid (dPSA) primarily function through targeted immunotherapy. Monoclonal antibodies such as SEAM 3 bind to the glycan on the cell surface and induce apoptosis in cancer cells [6, 7]. Antibody-drug conjugates (ADCs) like SAC-253 utilize dPSA as a docking site to deliver cytotoxic payloads directly into tumor cells [5]. Additionally, targeting dPSA can inhibit tumor cell adhesion and migration by disrupting its interaction with cell-surface proteins like nucleolin, and may block immune shielding mechanisms that allow tumors to evade the host immune system [1, 2, 5].