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Adeno-associated viral vector gene transfer into leptomeningeal xenografts

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Abstract

Leptomeningeal carcinomatosis is a painful and debilitating complicationof cancer. Indwelling reservoirs provide continuous assess tothe subarachnoid space, making leptomeningeal cancer potentially amenableto gene therapy. Adeno-associated virus (AAV) is adefective virus not associated with any human disease.We used an AAV vector to transduce medulloblastoma(DAOY) cells in a nude rat model ofleptomeningeal disease. After intraventricular injection of vector carryingthe bacterial lacZ gene, β-galactosidase positive cells werefound in the implanted tumor and in ependymaland subependymal cells but not in underlying normalbrain parenchyma. No evidence of virally-mediated toxicity wasnoted in the animals. The results of thispilot study demonstrate that AAV vectors may beused to transfer and express foreign genes inestablished leptomeningeal tumors.

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Authors and Affiliations

  1. Department of Neurology and the Cotzias Laboratory of Neuro-oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA

    Myrna R. Rosenfeld, Laura Schramm & Patricio I. Meneses

  2. Division of Child Neurology, Children‘s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

    Ira Bergman & Judith A. Griffin

  3. Department of Neurosurgery, Cornell University Medical Center, New York, New York, 10021, USA

    Michael G. Kaplitt

Authors
  1. Myrna R. Rosenfeld
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  2. Ira Bergman
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  3. Laura Schramm
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  4. Judith A. Griffin
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  5. Michael G. Kaplitt
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  6. Patricio I. Meneses
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Rosenfeld, M.R., Bergman, I., Schramm, L. et al. Adeno-associated viral vector gene transfer into leptomeningeal xenografts. J Neurooncol 34, 139–144 (1997). https://doi.org/10.1023/A:1005702228721

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