RRC ID |
4774
|
著者 |
Noguchi M, Imaizumi K, Kawabe T, Wakayama H, Horio Y, Sekido Y, Hara T, Hashimoto N, Takahashi M, Shimokata K, Hasegawa Y.
|
タイトル |
Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-gamma gene into lung cancer.
|
ジャーナル |
Cancer Gene Ther
|
Abstract |
CD40-CD40 ligand (CD40L) interaction is an important costimulatory signaling pathway in the crosstalk between T cells and antigen-presenting cells. This receptor-ligand system is known to be essential in eliciting strong cellular immunity. Here we demonstrate that murine lung cancer cells (3LLSA) transduced with the CD40L gene (3LLSA-CD40L) were rejected in syngeneic C57BL/6 mice, but grew in CD40-deficient mice to the same extent as control tumor cells. Immunohistochemical study showed that inflammatory cells, including CD4+, CD8+ T cells and NK cells, infiltrated into the inoculated 3LLSA-CD40L tumor tissue. Inoculation of 3LLSA-CD40L cells into mice resulted in the induction of 3LLSA-specific cytotoxic T-cell immunity, and the growth of parental 3LLSA tumors was inhibited when 3LLSA cells were inoculated into C57BL/6 mice mixed with 3LLSA-CD40L cells or when they were rechallenged 4 weeks after 3LLSA-CD40L cells were rejected. Furthermore, co-inoculation of interferon (IFN)-gamma-transduced cells (3LLSA-IFNgamma) with 3LLSA-CD40L cells enhanced the antitumor immunity efficiently in vivo. These results indicate that the in vivo priming with CD40L- and IFN-gamma gene-transduced lung cancer cells is a promising strategy for inducing antitumor immunity in the treatment of lung cancer.
|
巻・号 |
8(6)
|
ページ |
421-9
|
公開日 |
2001-6-1
|
DOI |
10.1038/sj.cgt.7700320
|
PMID |
11498762
|
MeSH |
Animals
CD40 Ligand / genetics*
Cancer Vaccines*
DNA, Complementary / metabolism
Genetic Therapy / methods*
Immunohistochemistry
Interferon-gamma / genetics*
Interferon-gamma / metabolism
Lung Neoplasms / genetics*
Lung Neoplasms / therapy*
Mice
Mice, Inbred C57BL
Recombinant Proteins / metabolism
Spleen / metabolism
T-Lymphocytes, Cytotoxic / metabolism
Time Factors
Transduction, Genetic*
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 |
遺伝子材料 |
pBluescript KS+mIFN gamma (RDB01482) |
ヒト・動物細胞 |
B16 melanoma 4A5(RCB0557) |