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273. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection or Gene-Activated Matrices for Gene Delivery - Preliminary Results of a Veterinary Clinical Study

Schillinger, Ulrike ; Schwarz, Bianca ; Kempf, Tina ; Jahnke, Anika ; Fischer, Cornelia ; Loecher, Anne ; Schlemmer, Stefanie ; Hirschberger, Johannes ; Brill, Thomas ; Koestlin, Roberto ; Gaensbacher, Bernd ; Plank, Christian

Molecular therapy, 2006-05, Vol.13 (S1), p.S105-S105 [Periódico revisado por pares]

Milwaukee: Elsevier Limited

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  • Título:
    273. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection or Gene-Activated Matrices for Gene Delivery - Preliminary Results of a Veterinary Clinical Study
  • Autor: Schillinger, Ulrike ; Schwarz, Bianca ; Kempf, Tina ; Jahnke, Anika ; Fischer, Cornelia ; Loecher, Anne ; Schlemmer, Stefanie ; Hirschberger, Johannes ; Brill, Thomas ; Koestlin, Roberto ; Gaensbacher, Bernd ; Plank, Christian
  • Assuntos: Antigens ; Cancer therapies ; Colorectal cancer ; Cytokines ; Drug dosages ; Fibrosarcoma ; Gene therapy ; Ligands ; Liver ; Melanoma ; Metastasis ; Surgery ; Tumors ; Vectors (Biology)
  • É parte de: Molecular therapy, 2006-05, Vol.13 (S1), p.S105-S105
  • 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 feline GM-CSF, IFN-g and IL-2 in combination, feline GM-CSF alone or human GM-CSF were administered. The study design is prospective, randomized, placebo- controlled (= standard therapy) and includes five arms: (1) standard therapy, i.e. surgery alone; (2) nonviral Magnetofection of the feline GM-CSF, IFN-g and IL-2 genes into the tumor before surgery or nonviral administration by Magnetofection of feline (3) or human GM-CSF (4) gene alone and (5) nonviral application of the feline GM-CSF, IFN-g and IL-2 genes by a gene-activated-matrix. The procedure included phase I dose finding studies for the gene therapy groups followed by a phase II. 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 (chemicell, Berlin, Germany) and gene delivery under the influence of a magnetic field (Scherer et al. 2002, Gene Ther., Plank et al. 2003, Biol. Chem). It was applied here in order to achieve improved retention of the injected vector dose in the tumor.Copolymer-protected gene vectors (Scherer et al. 2002, J. Gene Med. 4:634-643) were immobilized on a collagen sponge to achieve sustained localized matrix-mediated gene delivery. After tumor excision the gene-activated matrices were implanted in the tumor bed intrasurgically.Pre- and postsurgical diagnosis included complete clinical monitoring of the cats. All gene-therapeutic treatments were well tolerated and led to prolonged relapse-free survival (one year time points: 50 % for intrasurgical implantation of the vector-loaded collagen sponge in the tumor bed, and 52 % for presurgical Magnetofection with human GM-CSF versus 23 % for surgery alone). Additional patients have been admitted to the Magnetofection group such that long-term follow-up will warrant a profound assessment of the benefits of this treatment.
  • Editor: Milwaukee: Elsevier Limited
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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