Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study

J Vet Med A Physiol Pathol Clin Med. 2007 Dec;54(10):599-606. doi: 10.1111/j.1439-0442.2007.01002.x.


Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cat Diseases / therapy*
  • Cats
  • Dose-Response Relationship, Drug
  • Female
  • Fibrosarcoma / therapy
  • Fibrosarcoma / veterinary*
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods
  • Genetic Therapy / veterinary*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Interferon-gamma / genetics*
  • Interferon-gamma / immunology
  • Interleukin-2 / genetics*
  • Interleukin-2 / immunology
  • Magnetics
  • Male
  • Recombinant Proteins
  • Safety
  • Treatment Outcome


  • Interleukin-2
  • Recombinant Proteins
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor