| RRC ID |
39104
|
| 著者 |
Sumimoto H, Tani K, Nakazaki Y, Tanabe T, Hibino H, Wu MS, Izawa K, Hamada H, Asano S.
|
| タイトル |
Superiority of interleukin-12-transduced murine lung cancer cells to GM-CSF or B7-1 (CD80) transfectants for therapeutic antitumor immunity in syngeneic immunocompetent mice.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
Interleukin-12 (IL-12) is a heterodimeric cytokine that consists of p40 and p35 subunits. IL-12 has been regarded as a potent inducer of host antitumor immunity through interferon-gamma (IFN-gamma) production and development of Th1 helper T cells from Th0 cells. Here, we demonstrate the immunomodulatory actions of an IL-12-transduced murine lung cancer cell line, Lewis lung carcinoma (LLC) (LLC/IL12) cells, in syngeneic C57BL/6 mice. We also report on their therapeutic potency. Three LLC/IL12 cells producing different levels of IL-12 were cloned and found to have diminished tumorigenicity in C57BL/6 mice depending on their level of IL-12 production. In vivo depletion assay demonstrated that the loss of tumorigenicity of LLC/IL12 depended on both CD4+ and CD8+ T cells, and that natural killer (NK) cells were involved, especially in the early phase of immunity. The strong systemic antitumor immunity against challenge with wild type LLC (LLC/wt) cells was also induced by LLC/IL12 cells. The systemic antitumor memory was found to be dependent mainly on the CD4+ T-cell subset. 51Cr-release assay revealed that the killer activity consisted of a specific killer activity directed at the parental LLC/wt cells and a nonspecific killer activity directed at both LLC/wt and syngeneic EL-4 thymoma cells. In addition, LLC/IL12 apparently had a much stronger antitumor effect against the established LLC/wt tumor than LLC transduced with B7-1 or GM-CSF cDNA. IL-12 can be considered an efficient candidate molecule for immunogene therapy for lung cancer in this experimental system.
|
| 巻・号 |
5(1)
|
| ページ |
29-37
|
| 公開日 |
1998-1-1
|
| PMID |
9476964
|
| MeSH |
Animals
B7-1 Antigen / genetics*
B7-1 Antigen / immunology
CD4-Positive T-Lymphocytes / immunology
Carcinoma, Lewis Lung / immunology
Carcinoma, Lewis Lung / therapy*
Genetic Therapy*
Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
Granulocyte-Macrophage Colony-Stimulating Factor / immunology
Immunocompetence
Immunotherapy
Interleukin-12 / genetics*
Interleukin-12 / immunology
Lung Neoplasms / immunology
Lung Neoplasms / therapy*
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
T-Lymphocytes, Cytotoxic / immunology
Transfection
Tumor Cells, Cultured
|
| IF |
4.534
|
| 引用数 |
21
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
ONCOLOGY
GENETICS & HEREDITY
|
| リソース情報 |
| ヒト・動物細胞 |
|
