[Synergic effect of adenoviral vector-encoding human alpha-fetoprotein and interferon-gamma on immunity against hepatocellular carcinoma in mice].
OBJECTIVE
Primary hepatocellular carcinoma (HCC) is a common malignant tumor. Up to date, no effective treatment for HCC is available. This study was to investigate the synergic effect of adenoviral vector-encoding xenogeneic alpha-fetoprotein (AFP) and interferon-gamma (IFN-gamma) on the immunity against HCC in mice.


METHODS
IFN-gamma gene was cloned using reverse transcription-polymerase chain reaction (RT-PCR). Replication-defective adenovirus encoding both human AFP and murine IFN-gamma was constructed. The cytotoxic activity of antigen-specific cytotoxic T lymphocytes (CTLs) was detected 7 days after the intradermal immunization of C57BL/6 mice with Ad-hAFP, Ad-IFN-gamma or Ad-hAFP/IFN-gamma using standard (51)Cr release assay. The survival of mice after the subcutaneous inoculation of 5x10(6) hepatoma Hepa 1-6 cells was checked.


RESULTS
The cytotoxic activity of CTLs elicited by Ad-hAFP/IFN-gamma was much stronger than that by Ad-hAFP or Ad-IFN-gamma alone. At an effector:target (E:T) ratio of 10:1, the cytotoxic activities of CTLs in Ad-hAFP/IFN-gamma, Ad-hAFP, and Ad-IFN-gamma groups were (43.8+/-5.5)%, (28.2+/-3.2)%, and (12.8+/-1.9)%, at a ratio of 30:1, were (79.6+/-6.4)%, (51.9+/-4.3)%, and (15.6+/-2.3)%, and at a ratio of 90:1, were (88.2+/-6.3)%, (62.5+/-4.8)%, and (26.5+/-2.4)%, respectively. The tumor formation rates were 80% in Ad-hAFP-immunized mice and 100% in Ad-IFN-gamma-immunized mice at 2 months after inoculation with Hepa1-6 cells; no tumor formed in Ad-hAFP/IFN-gamma-immunized mice, and all mice in this group survived during two-month observation.


CONCLUSIONS
Ad-hAFP can efficiently induce immunity against HCC in mice, and IFN-gamma enhances such an effect.
Tan
Xiao-Hua
XH
Center for Gene Therapy, Department of Molecular and Pathological Medicine, Medical Center, McMaster University, Hamilton, ON. Canada, L8S. xiaohua_t@hotmail.com
Zhu
Qing
Q
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D000509:alpha-Fetoproteins / Q000235:genetics*
D000509:alpha-Fetoproteins; D007371:Interferon-gamma