| RRC ID |
37
|
| 著者 |
Ajiki T, Murakami T, Kobayashi Y, Hakamata Y, Wang J, Inoue S, Ohtsuki M, Nakagawa H, Kariya Y, Hoshino Y, Kobayashi E.
|
| タイトル |
Long-lasting gene expression by particle-mediated intramuscular transfection modified with bupivacaine: combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at a distant site.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
The immune response is modulated by genetic adjuvants using plasmid vectors expressing cytokines. Skeletal muscle can express a foreign gene intramuscularly administered via a needle injection, and the potential of muscle as a target tissue for somatic gene therapy in treating cancer has been explored. In the present study, we investigated the efficacy of particle-mediated intramuscular transfection modified with a local anesthetic agent, bupivacaine, on luciferase and green fluorescent protein. The results indicate that these proteins are more efficiently expressed and persist longer in muscle modified in this way compared with the needle-injection method. Using an established rat sarcoma model, particle-mediated intramuscular gene-gun therapy with a combination of IL-12 and IL-18 cDNA was conducted. Growth of the distant sarcoma was significantly inhibited by particle-mediated intramuscular combination gene therapy, and the survival rate was also improved. Furthermore, the combination gene-gun therapy maintained significant levels of interferon-gamma and induced a high activity of tumor-specific cytotoxic T lymphocytes. These results suggest that the sustained local delivery of IL-12 and IL-18 cDNA using intramuscular gene-gun therapy modified with bupivacaine can induce long-term antitumor immunity, and can provide the great advantage of inhibiting the disseminated tumor.
|
| 巻・号 |
10(4)
|
| ページ |
318-29
|
| 公開日 |
2003-4-1
|
| DOI |
10.1038/sj.cgt.7700575
|
| PII |
7700575
|
| PMID |
12679805
|
| MeSH |
Anesthetics, Local / therapeutic use*
Animals
Biolistics*
Bupivacaine / pharmacology
Bupivacaine / therapeutic use*
DNA, Complementary
Gene Expression
Genetic Therapy / methods*
Injections, Intramuscular
Interferon-gamma / blood
Interferon-gamma / metabolism
Interleukin-12 / genetics*
Interleukin-12 / metabolism
Interleukin-18 / genetics*
Interleukin-18 / metabolism
Kinetics
Male
Muscle, Skeletal / metabolism
Plasmids / administration & dosage
Rats
Rats, Inbred Lew
Sarcoma, Yoshida / immunology
Sarcoma, Yoshida / metabolism
Sarcoma, Yoshida / therapy*
Th1 Cells / immunology
Transfection
|
| IF |
4.534
|
| 引用数 |
20
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
ONCOLOGY
|
| リソース情報 |
| ラット |
|
