Mannan and anti-CD40 antibody decorated and tumor antigen, CpG and Poly I:C encapsulated poly lactic-co- glycolic acid (PLGA) nanoparticles loaded dendritic cells induced type I immune responses against prostate cancer ex vivo

Abstract

Abstract Purpose Cancer vaccines that stimulate the immune system to detect tumor-related antigens and trigger a T cell response have shown remarkable success in prostate cancer immunotherapy. In this study, we used PLGA nanoparticles and a carrier to deliver TCL, CPG-ODN, and Poly I:C to dendritic cells. We engineered the surface of the nanoparticles with mannan and anti-CD40 antibodies to specialize TCL delivery to dendric cells. We estimated different molecules and adjuvants' effects on DCs and T cell activation. Method In this study, Poly lactic-co-glycolic acid (PLGA) nanoparticles encapsulated with LNCaP cell line tumor antigens as well as Polyinosinic: polycytidylic acid (Poly: IC) and CpG-ODN as adjuvants. Mannan (MN) and Anti-CD40 antibody were then attached to the surface of PLGA nanoparticles. Monocyte-derived dendritic cells were generated, and on day 4, tumor cell lysate (TCL) and 8 different groups of nanoparticles were added to DCs to stimulate T lymphocytes and measure T cell response in vitro. Result Our results showed that using TCL, CpG-ODN, and Poly I:C encapsulated in nanoparticles and decorating the surface of nanoparticles with Mannan and anti-CD40 can induce maturation of dendritic cells and stimulate strong antitumor immune responses as well. Conclusion Therefore, combining TCL and adjuvants within nanoparticles and decorating them with Mannan and anti-CD40 enhances antitumor immune responses and can be considered an effective treatment strategy in prostate cancer.