3367

Herpes simplex virus (HSV) vectors are used in many type of cancer gene therapy trial. HSV has an efficacy of tumor selective cytotoxity against cancer cells with its oncolytic mechanism. But the efficacy of Viruses is limited by immune response that reduced transgene expression and decreased the efficacy of repeated vector administration. We demonstrated that lipofectamine-conjugated HSV reduced viral antigenicity in vivo, and showed higher transfection efficacy in vitro than virus alone. In the group of mice bearing metastatic liver tumor of mouse colon cancer (MC26), there was a tendency that mice injected with lipofectamine-conjugated HSV was survived for long term more than virus alone. (There was no statistic difference.) Several reports showed cationic lipid or molecules could bind to adenovirus and increase the efficacy of gene transfer to a variety of cells. In the electron microscopy, we found that lipofectamine stood close to cell surface membrane and many viruses could be seen inside of membrane of lipofectamine in the contrast with that only a few virus has been seen on the cell surface in the group of virus alone. We considered the lipofectamine helped viral transfection to cells. And we checked the viral antigenicity. In the evaluation of IgG in the blood of group of mice with lipofectamine-conjugated HSV showed less value than with viruses only. That means less immunogenic caused by the effect of lipofectamine. Hence, the lipofectamine reduced viral antigenicity, repeated administration could be allowed to attempt safer than virus alone. In the evaluation of IgM and IgE, there was no big difference between conjugated with or without. And, we injected lipofectamine-conjugated HSV or virus alone into the spleen of mice bearing metastatic liver tumor of MC26. Then DNA was extracted from liver and lung tissues of them. We found that virus’s DNA existed definitely more in the metastatic liver of MC26 than in the lung by PCR assay. This evidence was obviously seen in the group of mice treated by the injection of lipofectamine conjugated HSV. That means lipofectamine conjugated virus might be safer and more effective than virus alone.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]