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    Andrew M. Davidoff, MD

    Andrew M. Davidoff, MD

    Gene therapy reverses neuroblastoma growth in lab

    Researchers at St. Jude showed in mouse models of neuroblastoma that a virus engineered to carry the gene for an anti-cancer protein is an effective treatment for this tumor.

    The finding is important because it suggests that this technique might improve the treatment of neuroblastoma by offering a way to use the anti-cancer protein human interferon-beta (hIFN-beta) more effectively, while reducing treatment toxicity, according to Andrew Davidoff, MD, Surgery. Davidoff is senior author of a report on this work that appears in the August 15 issue of Clinical Cancer Research.

    The virus, called adeno-associated virus (AAV) carried the gene for hINF-beta to the liver, which used that gene to make hIFN-beta continuously at a low level, blocking the growth of blood vessels feeding the tumors. This treatment significantly restricted continued growth of established abdominal tumors; and it significantly prolonged survival for mice with established, disseminated disease. In addition, the combination of hINF-beta and infrequently administered, low doses of the chemotherapy drug cyclophosphamide caused established abdominal and disseminated tumors to get smaller.

    hIFN-beta most likely exerted its effect on blood vessels by reducing the activity of the genes for VEGF and bFGF, two proteins that stimulate vessel growth, said Davidoff. In the case of small tumors newly engrafted into the laboratory models, hIFN-beta appears to have also had a direct killing effect on the tumor cells.

    “This technique might be effective against a variety of solid tumors that are not necessarily vulnerable to direct cell-killing by hIFN-beta,” Davidoff said. “And the continuous, low-level expression of hIFN-beta that the genetically modified liver cells would generate could achieve therapeutic effectiveness while minimizing toxicity.”

    The paper’s other St. Jude authors include Paxton Dickson, MD, Cathy Ng, Christian Streck and Junfang Zhou of Surgery; and John Gray, Experimental Hematology.


    Last update: October 2005