| RRC ID |
73321
|
| 著者 |
Yamanaka R, Xanthopoulos KG.
|
| タイトル |
Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18.
|
| ジャーナル |
DNA Cell Biol
|
| Abstract |
We constructed pSin-SV40-HDV-SV40pA, an improved Sindbis DNA expression vector, and evaluated the potential of this vector system for brain tumor therapy. We investigated whether immunizing mice with xenogeneic DNA encoding human gp100 and mouse IL-18 would enhance the antitumor responses. To study the immune mechanisms involved in tumor regression, we examined tumor growth in B16-gp100-implanted brain tumor models using T-cell subset-depleted and IFN-gamma-neutralized mice. Hugp100/mIL-18 vaccination was also investigated for its antitumor effects against the wild-type murine B16 tumor, which expresses the murine gp100 molecule. Genetic immunization using plasmid pSin 9001 DNA codelivery of human gp100 and mouse IL-18 resulted in enhanced protective and therapeutic effects on the malignant brain tumors. The antitumor and protective effects were mediated by both CD4(+)/CD8(+) T cells and IFN-gamma. Vaccination with hugp100/mIL-18 conferred a significant survival merit to wild-type B16 tumor-harboring mice. Immunogene therapy with the improved Sindbis virus vector expressing xenogeneic gp100 and syngeneic IL-18 may be an excellent approach for developing a new treatment protocol. Thus, the Sindbis DNA system may represent a novel approach for the treatment of malignant brain tumors.
|
| 巻・号 |
24(5)
|
| ページ |
317-24
|
| 公開日 |
2005-5-1
|
| DOI |
10.1089/dna.2005.24.317
|
| PMID |
15869409
|
| MeSH |
Animals
Antigens, Neoplasm / genetics*
Antigens, Neoplasm / immunology
Brain Neoplasms / immunology
Brain Neoplasms / therapy*
Brain Neoplasms / virology
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology
Cancer Vaccines / immunology
Cancer Vaccines / therapeutic use*
Cytotoxicity Tests, Immunologic
DNA, Neoplasm / therapeutic use
DNA, Viral / genetics
Disease Models, Animal
Genetic Therapy / methods*
Genetic Vectors / administration & dosage
Genetic Vectors / genetics
Glioma / immunology
Glioma / therapy
Glioma / virology
Humans
Immunotherapy
Injections, Intramuscular
Interferon-gamma / biosynthesis
Interleukin-18 / genetics
Interleukin-18 / immunology
Interleukin-18 / therapeutic use*
Melanoma, Experimental / immunology
Melanoma, Experimental / therapy
Membrane Glycoproteins / immunology
Membrane Glycoproteins / therapeutic use*
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasm Proteins / immunology
Neoplasm Proteins / therapeutic use*
Neoplasm Transplantation
Sindbis Virus / genetics
Vaccination / methods
Vaccines, DNA / therapeutic use
gp100 Melanoma Antigen
|
| IF |
3.314
|
| リソース情報 |
| ヒト・動物細胞 |
B16 |
