Adenovirus vector encoding human KDR elicits immunity against hepatocellular carcinomas in mice / 中华肝脏病杂志
Chinese Journal of Hepatology
;
(12): 289-293, 2008.
Article
in Chinese
| WPRIM
| ID: wpr-332254
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of adenovirus vector encoding human vascular endothelial growth factor receptor-2 (hVEGFR-2 or hKDR) on breaking the immune tolerance and inducing immunity against murine hepatocellular carcinomas.</p><p><b>METHODS</b>Human and mouse KDR cDNA were cloned from human umbilical vein endothelial cells (HUVEC) and C57BL/6 mouse embryo cells respectively using RT-PCR, and then Ad hKDR and Ad mKDR were constructed. Seven days after immunization of the mice with Ad hKDR or Ad mKDR, an analysis of cytotoxic activity of antigen-specific cytotoxic T lymphocytes (CTL) was made by lactate dehydrogenase (LDH) release assay, in which splenocytes of the immunized mice acted as effectors and Hepa 1-6/mKDR cells as the targets. In addition, the survival of the mice immunized with Hepa 1-6 hepatoma cells was checked.</p><p><b>RESULTS</b>Seven days after immunization, the 6 h killing activities of CTL elicited by the Ad hKDR were 84.3%+/-6.7%, 71.5%+/-5.2%, and 44.6%+/-4.7% at the ratio of the effectorstargets (ET) of 1001, 501, and 251, respectively. Correspondingly, the CTL activities by Ad mKDR were 65.2%+/-6.1%, 46.7%+/-5.0%, and 22.6%+/-3.7%. Sixty percent of the Ad hKDR-immunized mice with 5*10(6) Hepa 1-6 hepatoma cells were still alive two months after the inoculation, whereas just 40% of the Ad mKDR-immunized mice with 2*10(6) Hepa 1-6 cells survived two months. When CD8+ or CD4+ T lymphocytes were deleted in the mice the above mentioned CTL activities and protection of the mice from tumors disappeared.</p><p><b>CONCLUSION</b>Adenovirus vector-mediated xenogeneic KDR can effectively break the immune tolerance to hepatocellular carcinomas in an animal model and induce a strong antigen-specific T cell response, which is dependent on CD8+ and CD4+ T cells.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transfection
/
T-Lymphocytes, Cytotoxic
/
CD4-Positive T-Lymphocytes
/
Adenoviruses, Human
/
Carcinoma, Hepatocellular
/
CD8-Positive T-Lymphocytes
/
Vascular Endothelial Growth Factor Receptor-2
/
Cell Line, Tumor
/
Allergy and Immunology
/
Genetics
Type of study:
Prognostic study
Limits:
Animals
/
Female
/
Humans
Language:
Chinese
Journal:
Chinese Journal of Hepatology
Year:
2008
Type:
Article
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