Gene therapy of experimental brain tumors using neural progenitor cells

Glioblastomas, the most frequent and malignant of primary brain tumors, hav e a very poor prognosis'. Gene therapy of glioblastomas is limited by the s hort survival of viral vectors and by their difficulty in reaching glioblas toma cells infiltrating the brain parenchyma. Neural stem/progenitor cells can be engineered to produce therapeutic molecules and have the potential t o overcome these limitations because they may travel along the white matter , like neoplastic cells, and engraft stably into the brain(2,3). Retrovirus -mediated transfer of the gene for interleukin-4 is an effective treatment for rat brain glioblastomas(4). Here, we transferred the gene for interleuk in-4 into C57BL6J mouse primary neural progenitor cells and injected those cells into established syngeneic brain glioblastomas. This led to the survi val of most tumor-bearing mice. We obtained similar results by implanting i mmortalized neural progenitor cells derived from Sprague-Dawley rats into C 6 glioblastomas. We also documented by magnetic resonance imaging the progr essive disappearance of large tumors, and detected 5-bromodeoxyuridine-labe led progenitor cells several weeks after the injection. These findings supp ort a new approach for gene therapy of brain tumors, based on the grafting of neural stem cells producing therapeutic molecules.