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 (Dox), a chemotherapeutic agent, on the human leukemia-bearing nude mice were investigated. An NIH3T3 fibroblast clone (NIH3T3-IFN-alpha +) secreting 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 IFN-alpha could be detected in the sera from the implanted mice. After the NIH3T3-IFN-alpha + 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-alpha + cells were implanted in combination with Dox. These results demonstrate that fibroblast-mediated human IFN-alpha gene therapy is effective in treating leukemia and may achieve a better therapeutic effect when combined with Dox.
Wang
J
J
Department of Immunology, Second Military Medical University, Shanghai, People's Republic of China.
Cao
X
X
Zhang
W
W
Ye
T
T
Tani
K
K
D016475:3T3 Cells; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D017690:Cell Transplantation; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007274:Injections, Intraperitoneal; D016898:Interferon-alpha / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014162:Transfection
D000903:Antibiotics, Antineoplastic; D016898:Interferon-alpha; D004317:Doxorubicin