TREATMENT OF LEUKEMIA WITH FIBROBLAST-MEDIATED INTERFERON-ALPHA GENE-THERAPY ALONE OR IN COMBINATION WITH DOXORUBICIN

The therapeutic effects of fibroblast-mediated human interferon-alpha (IFN-alpha) gene therapy, alone or in combination with Doxorubicin (Do x), a chemotherapeutic agent, on the human leukemia-bearing nude mice were investigated. An NIH3T3 fibroblast clone (NIH3T3-IFN-alpha(+)) se creting the highest level of human IFN-alpha(+) was obtained from the human IFN-alpha(+) gene-transfected fibroblasts. Three days after i.p. implantation of NIH3T3-IFN-alpha(+) cells, a certain level of human I FN-alpha could be detected in the sera from the implanted mice. After the NIH3T3-IFN-alpha(+) cells were implanted intraperitoneally into le ukemia-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-alpha(+) cells were impla nted in combination with Dox. These results demonstrate that fibroblas t-mediated human IFN-alpha gene therapy is effective in treating leuke mia and may achieve a better therapeutic effect when combined with Dox . Copyright (C) 1996 Elsevier Science Ltd.