ABSTRACT
To conduct an anti-tumor research by using targeted drug-loaded cell-derived microparticles to target the tumor microenvironment and enhance NK cell killing function. In this experiment, we obtained HepG2 tumor cell-derived microparticles by physical extrusion, high speed centrifugation and filtration, modified the hepatocellular carcinoma targeting peptide SP94 on the surface of microparticles and encapsulated the TGF-ß inhibitor SB505124. Finally we validated and analyzed whether the new drug delivery system can target to tumor site and enhance the anti-tumor function of NK cells. This type of novel targeted cell-derived microparticles drug delivery system will provide a novel idea for tumor immunotherapy.
Subject(s)
Carcinoma, Hepatocellular , Cell-Derived Microparticles , Liver Neoplasms , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Cell-Derived Microparticles/metabolism , Cell-Derived Microparticles/pathology , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Peptides , Pharmaceutical Preparations , Tumor MicroenvironmentABSTRACT
Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END+/Gal+-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.
