The synthesis of amphiphilic polyethyleneimine/calcium phosphate composites for bispecific T-cell engager based immunogene therapy

Abstract

Bispecific T-cell engagers (BiTEs) are single chain variable fragments with specific structures, which could connect the surface antigen on cancer cells and CD₃ ligands on T cells, and then engage the T cells for cancer immunotherapy. In this report, a novel organic–inorganic hybrid gene delivery system composed of stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to deliver MC.DNA into cells to express BiTE antibodies. This gene delivery system exhibits high transfection efficiency, long-term effects and low cytotoxicity in vitro. Furthermore, the gene production, anti-IGF1R/CD3 bispecific T-cell engager, exhibited a rapid redirection activity in T cells to induce cancer cell apoptosis. In summary, the results confirmed that stPEI-CaP could be an efficient gene delivery system for BiTE encoding MC.DNA based gene immunotherapy.