Tumor vaccine therapy against recrudescent tumor using dendritic cells simultaneously transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA.
Recently, dendritic cells (DC) transfected with tumor RNA have been used as a cancer vaccine. The efficacy of a cancer vaccine using DC transfected tumor RNA was examined. Of particular interest was whether a vaccine using DC transfected with recrudescent tumor RNA is effective for the treatment of a regrowing tumor after prior immunotherapy. In addition, the usefulness of co-transfection of granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA to augment the DC vaccine was examined. CT26 tumor-bearing mice were immunized by s.c. injection with DC transfected with CT26 mRNA (DC-CT26). The cytotoxic activity against CT26 in mice immunized with DC-CT26 was significantly higher than that in the control group (P < 0.001) and was augmented by GM-CSF mRNA co-transfection (P < 0.05), resulting in remarkable therapeutic efficacy in CT26 s.c. tumor models. Cytotoxic T lymphocytes induced by the vaccination using DC transfected with mRNA from the recrudescent tumor showed a potent cytotoxicity against the recrudescent CT26 tumor cells, which was significantly higher than the cytotoxicity induced by the vaccination using DC-CT26 (P < 0.05). In addition, in a recrudescent tumor model, this vaccination suppressed the regrowing s.c. tumors, and was augmented by GM-CSF mRNA co-transfection (P < 0.05). These results suggested that vaccination therapy using DC simultaneously transfected with whole tumor RNA and GM-CSF mRNA could generate therapeutic immune responses even against recrudescent tumor after prior vaccination.
Naka
Teiji
T
Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan.
Iwahashi
Makoto
M
Nakamura
Masaki
M
Ojima
Toshiyasu
T
Nakamori
Mikihito
M
Ueda
Kentaro
K
Katsuda
Masahiro
M
Miyazawa
Motoki
M
Ishida
Koichiro
K
Yamaue
Hiroki
H
D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000378:metabolism / Q000627:therapeutic use*; D012334:RNA, Neoplasm / Q000378:metabolism / Q000627:therapeutic use*; D054400:Receptors, CCR7 / Q000276:immunology; D013154:Spleen / Q000378:metabolism; D014162:Transfection
D051940:B7-2 Antigen; D019496:Cancer Vaccines; D012334:RNA, Neoplasm; D054400:Receptors, CCR7; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor