Schematic representation of CD47-targeted cancer immunogene therapy approach
(1) Polyplexes formed by linear polyethylenimine (LPEI) and plasmid DNA encoding for sCV1-hIgG1 are internalized by tumor cells via adsorptive endocytosis; (2) sCV1-hIgG1 fusion protein is expressed and secreted into the intercellular space; (3) sCV1-hIgG1 blocks CD47 on transfected and adjacent tumor cells and inhibits its interaction with SIRPα on immune cells; (4) the Fc part of sCV1-hIgG1 binds to Fc receptors on macrophages, dendritic cells (DCs), neutrophils, and NK cells, activating both the innate and the adaptive immune system; this together allows the eradication of tumor cells by immune effector cells.