PDPN CAR T cells

PDPN CAR T cells are an investigational, cell-based immunotherapy (biologic/adoptive cell therapy) in which patient or donor-derived T cells are genetically engineered via lentiviral transduction to express a chimeric antigen receptor (CAR) that targets podoplanin (PDPN) — a type I transmembrane mucin-like glycoprotein that is overexpressed in various solid tumors. The biological target is podoplanin (PDPN), which is abundantly expressed in several cancers including glioblastoma (particularly the mesenchymal subtype), squamous cell carcinoma, malignant mesothelioma, Kaposi sarcoma, angiosarcoma, and testicular seminoma. The CAR construct has been developed in multiple generations; early versions used an anti-pan-PDPN monoclonal antibody (NZ-1)-based single-chain variable fragment (scFv) with CD28, 4-1BB, and CD3ζ intracellular signaling domains (third-generation CAR), while more recent versions use an Lp2-based scFv designed to spare PDPN-expressing normal cells and reduce on-target/off-tumor toxicity. PDPN CAR T cells have demonstrated specific cytotoxicity against PDPN-positive glioblastoma (GBM) cells in vitro and have inhibited intracranial glioma xenograft growth in vivo. The therapy is primarily being investigated for glioblastoma, with research groups including those at Nagoya University (Japan) and the University of Würzburg (Germany) contributing to its development.

Other names

podoplanin-targeted CAR T cellsanti-PDPN CAR T cells