Podocalyxin-like protein 1 (tumor-restricted glycoform) (PODXL)

Podocalyxin-like protein 1 (PODXL) is a heavily glycosylated type I transmembrane sialomucin and a member of the CD34 family of glycoconjugates (UniProt O00592). In normal physiology, it is expressed on the apical surface of kidney podocytes, where its high negative charge maintains the filtration slits, and on vascular endothelial cells to regulate adhesion (Nielsen et al., 2007). However, in various aggressive cancers, PODXL is overexpressed and undergoes aberrant glycosylation, resulting in the presentation of a tumor-restricted glycoepitope characterized by terminal GalNAcβ1-containing O-glycans, such as LacDiNAc (Thomas et al., 2017). This specific glycoform acts as a neoantigen that promotes tumor cell motility, invasion, and epithelial-mesenchymal transition (EMT) by interacting with the actin cytoskeleton via adapter proteins like NHERF1/EBP50 (Snyder et al., 2020). Because this glycoepitope is absent in healthy tissues, it serves as a highly specific target for therapeutic interventions, such as the monoclonal antibody PODO447 and its derivative antibody-drug conjugates (ADCs), which aim to deliver cytotoxic agents directly to malignant cells while minimizing off-target toxicity to normal podocytes or endothelium (Snyder et al., 2020).

Other names

PodocalyxinPCLP-1Gp135PCLacDiNAc-PodocalyxinPODO447-targetTumor-restricted glycoepitope on Podocalyxin

Antibody-drug conjugate (ADC) mediated delivery of cytotoxic agents, Antibody-dependent cellular cytotoxicity (ADCC)