Treatment of leukemia with fibroblast-mediated interferon-alpha gene therapy alone or in combination with Doxorubicin

Abstract

The therapeutic effects of fibroblast-mediated human interferon-alpha (IFN-α) gene therapy, alone or in combination with Doxorubicin (Dox), a chemotherapeutic agent, on the human leukemia-bearing nude mice were investigated. An NIH3T3 fibroblast clone (NIH3T3-IFN-α +) secreting the highest level of human IFN-α + was obtained from the human IFN-α genetransfected fibroblasts. Three days after i.p. implantation of NIH3T3-IFN-α + cells, a certain level of human IFN-α could be detected in the sera from the implanted mice. After the NIH3T3-IFN-α + cells were implanted intraperitoneally into leukemia-bearing nude mice, the growth of leukemia was inhibited and the survival time of the leukemia-bearing mice was prolonged. The growth of leukemia was inhibited more obviously and the survival rate of the mice increased significantly when NIH3T3-IFN-α + cells were implanted in combination with Dox. These results demonstrate that fibroblast-mediated human IFN-α gene therapy is effective in treating leukemia and may achieve a better therapeutic effect when combined with Dox.