RESUMO
@#Objective To investigate the anti-melanoma immune effects of nano-tumor vaccine based on nano-adjuvant[CpG-coated nanoparticles(CNP)] and melanoma cell lysate antigen.Methods The immunoregulatory effects of CNP and melanoma cell lysate antigens on bone marrow-derived dendritic cells(BMDCs) and the regulatory effects on expression and secretion of cytokines IL-6 and IL-12 were investigated.After the mice inoculated with melanoma cells formed tumor,40C57BL/6N fermale mice with similar size of tumor were randomly divided into 4 groups:control(PBS) group,adjuvant(CNP) group,lysate(Lysate) group and vaccine(CNP+Lysate) group,which were administered subcutaneously once a week for 3 weeks.The tumor size of mice was recorded every 3 d and the tumor growth curve was drawn.The peripheral blood of mice was collected to detect the contents of IFN_γ and TNF_α,and immunohistochemical method was used to detect the infiltration of CD8~+T lymphocytes in tumor tissues.Results Compared with PBS,CpG and tumor lysate antigen groups,nano-vaccine adjuvant CNP effectively stimulated BMDCs maturation and promoted IL-6 and IL-12 secretion;Nanotumor vaccine showed good anti-tumor activity in vivo, the tumor size of mice in vaccine group decreased significantly,and the secretion levels of IFN_γ and TNF-α in serum were significantly higher than those in other groups;The infiltration of CD8~+T lymphocytes in tumor tissues of mice in vaccine group was also significantly better than that in other groups.Conclusion Nano-tumor vaccine effectively activated BMDCs,highly expressed immune factors,and also effectively inhibited tumor growth,showing good application potential.
RESUMO
Dendritic cells (DCs) play a pivotal role in T cell-mediated immunity and have been shown to induce strong antitumor immune responses in vitro and in vivo. Various approaches utilizing different vaccine cell formats, cell numbers, vaccination schedule, site of vaccination and maturation stages of DCs were investigated worldwide. While clinical trials have demonstrated the safety of such strategies, the clinical outcome was less than expected in most cases. This is due to in part host immunodeficiency imposed by tumors and immunoediting of tumor cells. To overcome these obstacles, new approaches to improve DC-mediated immunotherapeutic strategies are under investigation. First, functional enhancement of monocyte-derived DCs can be generated with using flt3-ligand (FL). Second, diverse antigenic determinants from heat shock-treated tumor cells may improve the immunogenicity of DC-based vaccines. Third, inclusion of ex vivo expanded NK/NKT cells in DC-based vaccines could be beneficial since the bidirectional interaction of these two cell types are known to enhance NK cell effector function and to induce DC maturation. Application of these approaches may induce a broadened antitumor immune response and thereby promote the elimination of tumor antigen-negative variant clones that had escaped immunosurveillance or undergone immunoediting. We are currently examining the feasibility of these immunotherapeutic approaches using a murine pancreatic cancer model system.