| RRC ID |
43492
|
| 著者 |
Inoue H, Iga M, Nabeta H, Yokoo T, Suehiro Y, Okano S, Inoue M, Kinoh H, Katagiri T, Takayama K, Yonemitsu Y, Hasegawa M, Nakamura Y, Nakanishi Y, Tani K.
|
| タイトル |
Non-transmissible Sendai virus encoding granulocyte macrophage colony-stimulating factor is a novel and potent vector system for producing autologous tumor vaccines.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
The recent clinical application of granulocyte macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor vaccines revealed substantial antitumor activity and valuable clinical results. However, for these vaccines to be optimally effective, the antitumor efficacies must be improved. Recently, Sendai virus (SeV) vectors, which are cytoplasmic RNA vectors, have emerged as safe vectors with high gene transduction. In the current study, the in vivo therapeutic antitumor efficacies of irradiated GM-CSF-transduced mouse renal cell carcinoma (RENCA) vaccine cells mediated by either fusion gene-deleted non-transmissible SeV encoding mouse GM-CSF (SeV/dF/G) or adenovirus (E1, E3 deleted serotype 5 adenovirus) encoding mouse GM-CSF (AdV/G) (respectively described as irRC/SeV/GM or irRC/AdV/GM) were compared in RENCA-bearing mice. The results showed that the antitumor effect was equivalent between irRC/SeV/GM and irRC/AdV/GM cells, even though the former produced less GM-CSF in vitro. The cell numbers of activated (CD80(+), CD86(+), CD80( (+) )CD86(+)) dendritic cells in lymph nodes from mice treated with irRC/AdV/GM or irRC/SeV/GM cells were increased significantly compared with those of mice treated with the respective controls, at both the earlier and later phases. In an in vitro cytotoxicity assay, splenocytes harvested from mice treated with both irRC/SeV/GM and irRC/AdV/GM cells showed tumor-specific responses against RENCA cells. The restimulated splenocytes harvested from mice treated with irRC/SeV/GM or irRC/AdV/GM cells produced significantly higher levels of interleukin-2, interleukin-4, and interferon-gamma compared with their respective controls (P < 0.05). Furthermore, vaccination with irRC/AdV/GM or irRC/SeV/GM cells induced significantly enhanced recruitment of the cytolytic effectors of CD107a(+)CD8(+) T cells and CD107a(+) natural killer cells into tumors compared with those induced by their respective controls (P < 0.05). Taken together, our results suggest that the SeV/dF/G vector is a potential candidate for the production of effective autologous GM-CSF-transduced tumor vaccines in clinical cancer immune gene therapy.
|
| 巻・号 |
99(11)
|
| ページ |
2315-26
|
| 公開日 |
2008-11-1
|
| DOI |
10.1111/j.1349-7006.2008.00964.x
|
| PII |
CAS964
|
| PMID |
18957055
|
| MeSH |
Adenoviridae / genetics
Adenoviridae / immunology
Animals
Cancer Vaccines / immunology
Cancer Vaccines / therapeutic use*
Carcinoma, Renal Cell / genetics
Carcinoma, Renal Cell / immunology
Carcinoma, Renal Cell / therapy*
Cell Line, Tumor
Female
Genetic Therapy / methods
Genetic Vectors*
Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
Granulocyte-Macrophage Colony-Stimulating Factor / immunology
Humans
Kidney Neoplasms / genetics
Kidney Neoplasms / immunology
Kidney Neoplasms / therapy*
Mice
Mice, Inbred BALB C
Sendai virus / genetics*
Transduction, Genetic
|
| IF |
4.966
|
| 引用数 |
13
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
OS-RC-2(RCB0735)
VMRC-RCW(RCB1963) |
