DLL3-targeted CAR-T therapy (circRNA-LNP)

DLL3-targeted CAR-T therapy (circRNA-LNP) is an experimental in vivo cell therapy designed for the treatment of small cell lung cancer (SCLC). The therapy utilizes circular RNA (circRNA) to encode a chimeric antigen receptor (CAR) that targets Delta-like Ligand 3 (DLL3), a protein frequently overexpressed on the surface of SCLC cells. To achieve in vivo generation of CAR-T cells, the circRNA is encapsulated within lipid nanoparticles (LNPs) conjugated with anti-CD5 antibodies, which direct the genetic payload specifically to T cells. This approach leverages the enhanced stability and translational efficiency of circRNA compared to linear mRNA. Preclinical studies, including those presented at AACR 2026, have demonstrated that this method can effectively produce functional CAR-T cells in vivo, leading to significant tumor regression and prolonged survival in SCLC mouse models with a favorable safety profile.

Other names

DLL3-targeted in vivo CAR-T therapyDLL-3-targeted in vivo CAR-T therapyDLL 3-targeted in vivo CAR-T therapycircRNA-LNP DLL3 CAR-T