Glioma therapy and real-time imaging of neural precursor cell migration and tumor regression

Authors

  • Khalid Shah PhD,

    Corresponding author
    1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
    2. Center for Molecular Imaging Research (CMIR), Massachusetts General Hospital, Harvard Medical School, Boston, MA
    • 5421CMIR, Massachusetts General Hospital-East, 13th Street, Building 149, Charlestown, MA 02129
    Search for more papers by this author
  • Emilie Bureau MSc,

    1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Dong-Eog Kim MD,

    1. Center for Molecular Imaging Research (CMIR), Massachusetts General Hospital, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Katherine Yang BSc,

    1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Yi Tang MD,

    1. Center for Molecular Imaging Research (CMIR), Massachusetts General Hospital, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Ralph Weissleder MD, PhD,

    1. Center for Molecular Imaging Research (CMIR), Massachusetts General Hospital, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Xandra O. Breakefield PhD

    1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
    2. Center for Molecular Imaging Research (CMIR), Massachusetts General Hospital, Harvard Medical School, Boston, MA
    Search for more papers by this author

Abstract

Despite many refinements in current therapeutic strategies, the overall prognosis for a patient with glioblastoma is dismal. Neural precursor cells (NPCs) are capable of tracking glioma tumors and thus could be used to deliver therapeutic molecules. We have engineered mouse NPCs to deliver a secreted form of tumor necrosis factor–related apoptosis–inducing ligand (S-TRAIL); S-TRAIL is optimized to selectively kill neoplastic cells. Furthermore, we have developed means to simultaneously monitor both the migration of NSCs toward gliomas and the changes in glioma burden in real time. Using a highly malignant human glioma model expressing Renilla luciferase (Rluc), intracranially implanted NPC-FL-sTRAIL expressing both firefly luciferase (Fluc) and S-TRAIL was shown to migrate into the tumors and have profound antitumor effects. These studies demonstrate the potential of NPCs as therapeutically effective delivery vehicles for the treatment of gliomas and also provide important tools to evaluate the migration of NPCs and changes in glioma burden in vivo. Ann Neurol 2005;57:34–41

Ancillary