CCN-EV

CCN-EV is an engineered, virus-mimicking extracellular vesicle (EV) platform designed for the in vivo generation of multiplexed chimeric antigen receptor (CAR)-immune cells to treat bladder cancer. Developed by researchers at Sun Yat-sen Memorial Hospital, CCN-EV is engineered by knocking down NINJ1 in producer 293T cells to enhance mechanical stability and loading efficiency, co-expressing Cocal vesiculovirus glycoprotein (COCV-G) to facilitate membrane fusion and endosomal escape, and displaying single-chain variable fragments (scFvs) targeting CD3 (for circulating T cells) as well as CD103 and CD49a (for tissue-resident lymphocytes). The extracellular vesicles are loaded with mRNA encoding a multifunctional cargo: a HER2-targeting CAR for tumor-specific recognition, interleukin-12 (IL-12) to promote T-cell recruitment and activation, and matrix metalloproteinase-9 (MMP-9) to degrade the tumor extracellular matrix.