Engineering Tumor Cells with Tumor Necrosis Factor alpha (TNF-alpha) or CD40 Ligand (CD40L) Genes Induce Anti-tumor Immune Responses

摘要

One of the main problems in tumor therapy is immunosuppressive microenvironment of the tumor. To overcome this, we assessed targeted tumor cells with tumor necrosis factor- (TNF-) or CD40 Ligand (CD40L) to improve antigen presenting cells function and subsequently anti-tumor responses. 4T1 tumor cells were transfected with TNF- and CD40L genes using lipofectamine and chitosan nanocomplexes. Engineered tumor cells were assessed in vitro and in vivo. Results showed that chitosan nanoparticles delivery of TNF- or CD40L to 4T1 co-cultured with DCs induced expression of DCs co-stimulatory markers and enhanced the secretion of pro-inflammatory mediators IL-6, TNF- and IL-12. The DCs were also able to enhance expansion of T cells with enhanced IFN- and decreased IL-4 production. TNF- or CD40L engineered 4T1 cells resulted into delay in tumor growth. The study shows that nanoparticle manipulation of tumor cells by TNF- or CD40L induce anti-tumor immune responses. Then, strategies that apply chitosan nanoparticles could provide a potent tool for tumor targeting and treatments.