부산대학교 도서관

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-α (TNF-α) or CD40 Ligand (CD40L) to improve antigen presenting cells function and subsequently anti-tumor responses. 4T1 tumor cells were transfected with TNF-α 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-α 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-α and IL-12. The DCs were also able to enhance expansion of T cells with enhanced IFN-γ and decreased IL-4 production. TNF-α or CD40L engineered 4T1 cells resulted into delay in tumor growth. The study shows that nanoparticle manipulation of tumor cells by TNF-α or CD40L induce anti-tumor immune responses. Then, strategies that apply chitosan nanoparticles could provide a potent tool for tumor targeting and treatments. [ABSTRACT FROM AUTHOR]