A novel combination of suicide gene therapy and histone deacetylase inhibitor for treatment of malignant melanoma

作者：Yamamoto S; Yamano T; Tanaka M; Hoon DSB; Takao S; Morishita R; Aikou T; Kaneda Y^*

来源：Cancer Gene Therapy, 2003, 10(3): 179-186.

DOI：10.1038/sj.cgt.7700551

• suicide gene therapy
• histone deacetylase inhibitor
• melanoma
• nonviral gene delivery

One major problem associated with application of gene therapy to treatment of tumors is poor transgene expression. Although suicide gene therapy with the herpes simplex virus-thymidine kinase gene (HSV-tk) followed by administration of ganciclovir (GCV) was effective in the treatment of melanoma, it was still difficult to induce complete remission to cancer. A novel histone deacetylase inhibitor drug FR901229 was found to enhance transgene expression in tumor cells both in vitro and in vivo. Combination therapy with HSV-tk/GCV and FR901228 by direct injection into tumor enhanced antimelanoma effects. The number of apoptotic cells in melanoma tumors was increased significantly (P<.05) after combined suicide gene therapy and FR901228. Six times injection of HSV-tk/GCV and FR901228 prolonged mice survival compared to that of HSV-tk/GCV injection alone (P=.021). In total, 56% (10 of 18) of the mice survived 120 days after combined suicide gene therapy and FR901228 treatment, and no new tumors appeared in the surviving mice. However, only 19% (3 of 16) of the mice survived when treated with suicide gene therapy alone. This novel strategy may be applicable as a therapeutic regimen for the treatment of aggressive types of cancers.

• 出版日期2003-3