LF28z

LF28z is an experimental ligand-based chimeric antigen receptor (CAR) T-cell therapy designed to target **CD70** (also known as CD27 ligand), a protein frequently overexpressed in **glioblastoma** (GB) and other malignancies. Unlike traditional CARs that use a single-chain variable fragment (scFv) for antigen recognition, LF28z utilizes the **full-length (LF)** extracellular domain of **CD27**, the natural ligand for CD70, as its binding domain. The signaling architecture of the construct includes a **CD28** costimulatory domain and a **CD3ζ** activation domain. In preclinical comparative studies, LF28z demonstrated potent antigen-specific cytotoxicity and high lytic activity against glioblastoma cells in vitro and in 3D cerebral organoids. However, it was found to exhibit higher levels of T-cell exhaustion markers (such as PD-1) and lower Th1 cytokine secretion compared to other constructs like CD27z, which lacks the additional CD28 domain. The therapy is being investigated as a potential treatment for recurrent glioblastoma to overcome tumor heterogeneity and the immunosuppressive microenvironment.