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573. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection for Gene Delivery – Preliminary Results of a Veterinary Clinical Study

Schillinger, Ulrike ; Kjaergaard, Niels ; Wiedmann, Kathrin ; Loecher, Anne ; Schlemmer, Stefanie ; Schwarz, Bianca ; Kempf, Tina ; Hirschberger, Johannes ; Koestlin, Roberto ; Plank, Christian ; Gansbacher, Bernd ; Brill, Thomas

Molecular therapy, 2004-05, Vol.9 (S1), p.S216-S216 [Periódico revisado por pares]

Milwaukee: Elsevier Inc

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  • Título:
    573. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection for Gene Delivery – Preliminary Results of a Veterinary Clinical Study
  • Autor: Schillinger, Ulrike ; Kjaergaard, Niels ; Wiedmann, Kathrin ; Loecher, Anne ; Schlemmer, Stefanie ; Schwarz, Bianca ; Kempf, Tina ; Hirschberger, Johannes ; Koestlin, Roberto ; Plank, Christian ; Gansbacher, Bernd ; Brill, Thomas
  • É parte de: Molecular therapy, 2004-05, Vol.9 (S1), p.S216-S216
  • Descrição: Feline fibrosarcoma is one of the most common feline tumors. It arises spontaneously, is rarely metastatic and relapses within 6 months after standard therapy (surgical resection) in 75% of the cases. This makes it an ideal model for evaluating immunostimulatory therapeutic strategies. Moreover, besides aggressive surgical excision no effective and versatile treatment is available.Here we report preliminary results from a comparative clinical study where the genes for human IL-2, feline IFN-γ, or human GM-CSF, respectively, alone or in combination, were administered. The study design is prospective, randomized, placebo-controlled (= standard therapy) and comprises five arms: (1) standard therapy, i.e. surgery alone; (2) administration of adenovirus coding for IL-2/IFN-γ or (3) IFN-γ alone into the tumor bed after surgery; (4) presurgical intra-tumoral injection of adenovirus coding for IL-2/IFN-γ and (5) nonviral Magnetofection of the human GM-CSF gene into the tumor before surgery. The procedure included phase I dose finding studies for the gene therapy groups followed by a phase II comprising 20 patients per group. Preliminary clinical endpoint is relapse-free survival for one year.Magnetofection, which has been developed in our laboratory, is the association of vectors with magnetic particles and gene delivery under the influence of a magnetic field (Scherer et al. 2002, Gene Ther. 9:102-109; Plank et al. 2003, Biol. Chem. 384:737-747). It was applied here in order to achieve improved retention of the injected vector dose in the tumor and in order to eventually achieve better tissue penetration by the vector. Plasmid DNA with the GM-CSF gene under the control of the CMV promoter was associated with polyethylenimine-coated magnetic particles (chemicell, Berlin, Germany), and a dose corresponding to 1250 μg DNA in a volume of 500 μl saline was administered twice in a one week interval prior to surgery into the biologically active margins of the fibrosarcoma. A neodymium-iron-boron permanent magnet was fixed on the tumor adjacent to the injection sites during one hour after vector injection. Pre- and postsurgical diagnosis included monitoring for toxicity, fever, blood cell count, for some treatments serum cytokine levels and evaluation of cytokine expression in tumors. The expression of the cytokine genes was demonstrated for all treatments. All gene-therapeutic treatments led to prolonged relapse-free survival (one year time points: 50% for postsurgical adenovirus administrations into the tumor bed, 37% for presurgical intratumoral adenovirus administrations, and 52% for presurgical Magnetofection versus 23% for surgery alone). Among the evaluated treatments Magnetofection is the most versatile, most cost-effective, and most relevant in veterinary practise as it avoids the legally required safety precautions associated with the use of recombinant viruses. With further patients admitted to the study, long-term follow-up will warrant a profound assessment of the benefits of this treatment.
  • Editor: Milwaukee: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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