Short term-neuropathological aspects of in vivo suicide gene transfer to the F98 rat glioblastoma using liposomal and viral vectors

• von Eckardstein, K. ^[1] ; Patt, Stephan ^[2] ; Zhu, J. ^[3] ; Zhang, L. ^[3] ; Cervós-Navarro, J. ^[4] ; Reszka, R. ^[3]
  1. [1] Institute of Neuropathology, Free University Berlin, Berlin, Germany, 2M ax-Del bruck-Center for Molecular Medicine (MOC), Berlin, Germany, 30epartment of Neurosurgery, Klinikum Buch, Berlin, Germany
  2. [2] Institute of Neuropathology, Free University Berlin, Berlin, Germany; 1nstitute of Pathology (Neuropathology), Friedrich Schiller University Jena, Jena, Germany
  3. [3] Max-Del bruck-Center for Molecular Medicine (MOC), Berlin, Germany
  4. [4] Institute of Neuropathology, Free University Berlin, Berlin, Germany; 1nternational University Catalunya, Barcelona, Spain

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 16, Nº. 3, 2001, págs. 735-744
• Idioma: inglés
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  • To date, only few preclinical protocols on liposomal suicide gene transfer in tumors have been published, none of which directly compared viral to liposomal vectors in terms of immunoreactivity and efficacy. We thus studied the neuropathological alterations in 80 rats being treated for glioblastoma using liposomal and, for comparison, adenoviral and retroviral suicide gene transfer approaches to identify vectorassociated efficacy and toxicity for further clinical studies. 62 rats served as controls. F98 tumors were established in Fisher rats and transfected in vivo with the thymidine kinase gene of herpes simplex virus (HSVtk) by a single intratumoral application and an implanted intratumoral continuous delivery system. Three days later ganciclovir wa given intraperitoneally for 14 days.

    The animals were sacrificed 17 days post completed gene transfer. Brains were examined histologically and immunohistochemicaJIy using markers for immunocompetent cells. Ten animals showed complete tumor regression; they all belonged to the liposomal and adenoviral groups. In 6 of 10 experimental groups considerable numbers of lymphocytes along the margins of the regression cavities could be observed. Control animals of the liposomal and adenoviral groups showed only little lymphocytic infiltration, underlining the minimal immunogenicity of these carriers. In contrast, the retroviral control group featured a high lymphocyte infiltration. In summary, this study indicates that, in terms of both efficacy and immunoreaction, liposomes are as appropriate as adenoviruses in the treatment of rat glial tumors using suicide gene transfer strategies.