Umbilical cord blood-derived dendritic cells loaded with BGC823 tumor antigens and DC-derived exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumor immunity in vitro and in vivo

BACKGROUND: Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells and from which a significant number of dendritic cells (DCs) can be produced. But the therapeutic role of DCs and exosomes (EXO) generated from DCs is not fully elucidated. MATERIAL AND METHODS: The UCB-derived DCs were loaded with tumor antigens generated from BGC823 cell line. Exosomes were derived from these DCs by ultracentrifugation. Dendritic cells and DCex were evaluated by light microscope, transmission electron microscope (TEM), flow cytometry, and western blot assay. The therapeutic role of DCs and EXO generated from DCs were then detected in vitro and in vivo. RESULTS: Dendritic cells isolated from umbilical cord blood after loading with tumor antigens generated from BGC823 cell line could express high levels of protein molecules: MHC-I, MHC-II, CD34, CD40, CD80, CD86, CD11c and CD54 and mediate a stronger promotion of T cells proliferation. And, they could also enhance the cytotoxicity effects of the generated CTL in vitro and in vivo. Exosomes isolated from these DCs were 40-90-nm round particles with a complete membrane structure and could also expressed molecules similar to DCs. Exosomes could stimulate T cell proliferation, produce effective cytotoxicity and induce more efficient in vivo antitumor immunity. CONCLUSIONS: These results suggested that tumor antigens loaded DCs derived from unrelated umbilical cord blood or DCex can induce tumor specific cytotoxicity and this may represent a novel immunotherapy for tumors. Because of their advantage of stable, easy to store, DCex have a more brilliant prospects in the tumor immunity. ADDITIONAL INFORMATION: We reported that exosomes derived from umbilical cord blood dendritic cell (UBDC), similar to DCs, can trigger activation of T cells significantly. These data demonstrate that DC-derived exosomes (DCex) can mediate essential adaptive immune functions.