Specific antitumor effects of tumor vaccine produced by autologous dendritic cells transfected with allogeneic osteosarcoma total RNA through electroporation in Rats

Abstract

OBJECTIVE: Transfection of dendritic cells with tumor-derived RNA has recently been shown

to elicit tumor-specific CTL capable of recognizing and lysing a variety of tumor cells. However,

the integration of allogeneic osteosarcoma mRNA and autologous DCs has not been fully

examined. This study was designed to investigate the antitumor effects of tumor vaccine produced

by autologous dendritic cells transfected with allogeneic osteosarcoma total RNA through

electroporation in tumor-bearing rats model. 

METHODS: In the present study, we transfected Wistar rat osteosarcoma cells derived total RNA

to SD rat bone marrow-derived DCs through electroporation. The tumor vaccine was applied to in

tumor-bearing rats model and the specific antitumor effects of the tumor vaccine were observed.

Then CTL activity was evaluated one week after the first immunization of SD rats with

electroporated DCs and the specificity of the cytotoxic activity was confirmed in cold target

inhibition assays and using mAbs blocking MHC class I or CD8 molecules.  

RESULTS: The immunization using autologous DCs electrotransfected with allogeneic

osteosarcoma total RNA induced UMR106-specific CTL responses which were statistically

significant and the cytotoxic activity was inhibited by the treatment with anti-CD8 and

anti-MHC-class I monoclonal antibodies. In in vivo experiments, 80% of the rats immunized with

allogeneic osteosarcoma RNA transfected to DCs were typically able to reject tumor challenge

and remained tumor-free. Vaccinated survivors developed long immunological memory and were

able to reject a subsequent rechallenge with the same tumor cells but not a syngeneic unrelated

tumor line. 

CONCLUSION：The present study provided valid evidence of integration of rat allogeneic

tumor-derived mRNA and autologous DCs through electroporation and confirmed this novel

tumor vaccine have the potential to induced osteosarcoma-specific CTL response and reject

osteosarcoma challege. This technique and its products may thus represent a promising strategy

for DC-based immunotherapy of patients with osteosarcoma.