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


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.


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.


CONCLUSIONS
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.
Yu
Zhe
Z
Center of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi China.
Sun
Honghui
H
Zhang
Ting
T
Yang
Tongtao
T
Long
Hua
H
Ma
Bao'an
B
D000818:Animals; D001859:Bone Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines / Q000276:immunology*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D018274:Electroporation; D005240:Feasibility Studies; D007167:Immunotherapy; D008297:Male; D012516:Osteosarcoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000276:immunology* / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines; D012333:RNA, Messenger; D012334:RNA, Neoplasm