Adoptive Immunotherapy with Cytokine Gene-modified Cytotoxic T Lymphocytes

Abstract

Adoptive immunogene therapy of cancer is not widely studied, although it has been proposed as a promising strategy for cancer gene therapy. One of the major obstacles to this approach is the difficulty in introducing cytokine genes efficiently into T lymphocytes. We developed adoptive immunotherapy models with murine tumor-specific cytotoxic Tlymphocytes (CM). By using adenoviral vectors, we achieved up to 100% gene transduction of murine T lymphocytes. Treatment of mice with the CTL genetically modified to produce IL-2 resulted in reduction of tumor metastasis and longer survival from intracerebral tumor death. Through a comparative study on the antitumor effects of CTL genetically modified with a variety of cytokine genes, transduction with interferon-g gene showed a prominent increase in therapeutic efficacy of CTL in both metastatic and subcutaneous tumor models. Further additive effect was obtained by the adoptive cellular therapy in combination with vaccination of cytokine gene-modified tumor cells. Our findings provide a hopeful strategy of adoptive immunotherapy for human cancers.