Specific antitumor effects of tumor vaccine produced by electrofusion between osteosarcoma cell line and dendritic cells in rats

Abstract

Background: Dendritic cells (DCs) are the strongest antigen presenting cells (APCs). They can present antigen to T lymphocytes in vivo and in vitro, and induce cytotoxic T lymphocyte (CTL) reactions. This study was designed to investigate the immunologic potency and antitumor effecs of tumor vaccine produced by electrofusion between rat osteosarcoma cells and DCs. Methods: DCs obtained from rat bone marrow were propagated in vitro under the condition of rGM-CSF, rIL-4 and rTNF-α and were purified by monoclonal antibody OX62 and magnetic beads. Then the UMR-106 cell line was fused with DCs to produce the tumor vaccine and the specific antitumor effects of the tumor vaccine were observed. Results: A comparison of electrofusion products generated with allogeneic versus syngeneic DCs was conducted. 70% of the rats immunized with allogeneic electrofused cells were typically able to reject tumor challenge and remained tumor-free, while 50% in the syngeneic group. Vaccinated survivors developed long immunological memory. 7 weeks after the second challenge, all the immunized rats survived. The therapeutic potential of this type of approach was suggested by the ability of UMR106-DC electrofusion products to induce tumor rejection in a substantial percentage of hosts (60%) bearing pre-established tumor cells. Interpretations: Treatment with electrofused tumor cells and allogeneic DCs might be capable of inducing a potent antitumor response and could conceivably be applied to a wide range of cancer indications for which tumor-associated antigens have not been identified.