Combination Gene Therapy of Herpes Simplex Virus Thymidine Kinase and Cytokines in Lung Cancer / 결핵
Tuberculosis and Respiratory Diseases
;
: 135-146, 2001.
Article
in Korean
| WPRIM
| ID: wpr-36114
ABSTRACT
BACKGROUND:
One of the important mechanisms responsible for a tumor escaping the immune response is an absence of the tumor associated antigen (TAA) on the cancer cell surface. To overcome this, combination gene therapy using a herpes simplex thymidine kinase (HSTK) gene, prototype of drug sensitizing gene, was conducted to enhance TAA release by cell destruction, as well as the cytokine genes for immune cell attraction.METHODS:
We investigated whether or not transduction with the adenovirus-HSTK (Ad-HSTK) enhanced the sensitivity of Lewis lung carcinoma (LLC) to ganciclovir (GCV) and induced a bystander effect. A Tumor vaccine trial was performed using LLC with ad-HSTK ±ad-GM-CSF±ad-IL-2 to determine if they exhibit some antitumor effect on established lung cancer xenografts.RESULTS:
LLC with ad-HSTK revealed a much higher sensitivity to ganciclovir (GCV). LLC transduced with ad-HSTK and/or ad-IL-2, ad-GM-CSF showed a lower in vivo tumorigenicity. In the treatment experiment, vaccination with LLC transduced with ad-HSTK, ad-IL-2, or ad-GM-CSF alone modestly suppressed the growth of an established tumor. Combined transduction with HSTK and GM-CSF induced stronger growth suppression of a established lung cancer, while HSTK and IL-2 combination transduction did not have any antitumor effect on individual transduction. Vaccination with LLC-HSTK-GM-CSF increased the infiltration of dendritic cells in the spleen.CONCLUSION:
It was concluded that a tumor vaccine transduced with HSTK and GM-CSF induces strong antitumor immunity by activating the dendritic cells.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphotransferases
/
Spleen
/
Thymidine Kinase
/
United Nations
/
Dendritic Cells
/
Genetic Therapy
/
Ganciclovir
/
Adenoviridae
/
Cytokines
/
Granulocyte-Macrophage Colony-Stimulating Factor
Limits:
Animals
Language:
Korean
Journal:
Tuberculosis and Respiratory Diseases
Year:
2001
Type:
Article
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